Following is our suggested itinerary, please note that you may extend the number of nights in each city:

Day 1: Madrid
Madrid is a city of great contrast and tendencies that provide a feast for the eyes: the Old City, the innumerable churches and convents, the Madrid of the Hapsburgs, the Royal Palace, the Puerta de Alcala, the Retiro Park, etc. Every façade, corner, statue or park has its own particular charm. It`s museum mile offers more masterpieces per square foot than anywhere else in the world; the stellar Prado with its El Grecos and Velazquezes; the Caravaggios and Rembrandts at the Thyssen-Bornemisza; and the Dalís, Mirós and Picasso's wrenching Guernica, at the Reina Sofía.
(Madrid to Tordesillas - 115 miles ? 2 hours)

Day 2:  Tordesillas
The Fertile Plain
Right next to some of the finest wineries of the officially certified and renowned Ribera del Duero region, is the historic town of Tordesillas. It is set on the banks of the Duero River, in surroundings of outstanding natural beauty. Stately homes and palaces bear witness to the importance once held by the court in the life of the town. Tordesillas is a fascinating town whose place in history is secure for two reasons: firstly, because after a series of difficult negotiations, Spain and Portugal met here to sign the Treaty of Tordesillas. This agreement drew a line in the Atlantic Ocean dividing the new lands which were being discovered in Africa and America between the two powers. The second reason is rather more romantic: after the death of her husband, Queen Juana I, known as "Juana la Loca" (Mad Juana) because she was said to have been driven crazy by love, retired to Tordesillas in 1509. She remained there in a palace-fortress until her death in 1555. A visit to Tordesillas brings this fascinating period of Spanish history to life. This province is home to the finest wineries of the Rueda region, most of which can be visited with organized wine-tasting.
(Tordesillas to Zamora - 43 miles - 1 hour)

Day 3 and 4:  Zamora
Sweet Highlands
We enter the province of Zamora by way of the region of Lands of Bread and Wine. A visit to the town of Toro, as fertile as it is historical, en route is a must. The old-world town of Zamora lies on a rocky hill above the Río Duero. With its numerous Romanesque churches of the 12th and 13th centuries it has been called a "museum of Romanesque art?. Stroll along the main square, Plaza Canovas; cross the arched Romanesque bridge from the 1300s; and take in at least some of the Romanesque churches for which the town is known, many dating from the 12th century. Don?t miss the Cathedral San Salvador. It is topped by a gold-and-white Eastern-looking dome. Inside, you'll find rich hangings, interesting chapels, two 15th-century Mudéjar pulpits, and intricately carved choir stalls. A visit is made even more complete if you stay in the Renaissance palace which now houses the Parador.
(Zamora to Salamanca - 40 miles - 1 hour)

Day 5:  Salamanca
Salamanca Grasslands
After discovering some of Spain's finest wines, Salamanca provides a feast of art and architecture to finish the route with, a city where the hustle and bustle of University life has gone undisturbed since the 16th century. Salmántica belonged to the Roman province of Lusitania, was besieged by Hannibal, conquered by the Arabs, lost and recuperated several times by the Christians, and definitively reconquered by the great pro-European king Alfonso VI.  Pre-Roman remains can be found in Teso de San Vicente, beside the river Tormes, in the Verraco (Iberian statue representing a bull) situated in the centre of the Roman Bridge, in the city walls, in numerous inscriptions and along the Calzada de la Plata. In 1200 Alfonso IX founded what was to become eighteen years later the University of Salamanca. Salamanca is a city of the golden glow.  Luscious hues of ever- changing honey and copper reflect off the sandstone walls of Spain's oldest university and numerous churches.  The Plaza Mayor and the Casa de las Conchas (house of conch shells), the Plaza de Anaya - all gather and return the wondrous play of light in this splendid city. The congruency and perfect "fit" of its stone architecture creates a beauty unsurpassed in any other city in Spain.  
(Salamanca to Madrid - 130 miles - 2 hours and 40 minutes)

Day 6:  Madrid
Spend your last day enjoying Madrid.