Background: The predicting of pituitary tumor behavior remains one of the most incurable medical problems. One of the causes is poor correlation between the morphology of pituitary tumors and their clinical aggressiveness. Material and methods: 96 cases included in our study have been microscopically investigated on specimens colored with eosin haematoxylin by three experienced pathologists according to WHO recommendations. Out of these ten cases were represented by normal pituitary tissue to make it possible to compare the typical pituitary morphology with the microscopic appearance of various types of pituitary adenomas. results: In both the normal pituitary gland and in pituitary adenomas, endothelial cells presenting a nuclear expression for S100 were occasionally observed. The percentage of positive cases for protein S100 was 66.12% from the total number of cases. Amongst these, 39.02% presented a compact growth pattern, 39.04% were of papillary type, 9.75% presented a trabecular growth pattern, 4.87% spindle-shaped and 7.31% were of alveolar type. Papillary type pituitary adenomas registered the highest intensity of expression for protein S100 in tumor cells. The acidophilic cells were present in a percentage of 34.2% of cases. Pituitary adenomas with basophilic cells represented a percentage of 26.8% of positive cases for protein S100, and, for 39% of cases the chromofobe component was present forming pure chromofobe pituitary adenomas or mixed chromofobe-acidophilic/basophilic pituitary adenomas. conclusions: Protein S100 expressions in tumor cells is implicated in the pathogenesis of the growth hormone and prolactin secreting pituitary adenomas, the mechanisms of activation being nowadays incompletely studied. Through analogy with the observations obtained in other tumor types, it is possible that S100 pituitary adenomas to represent a group of pituitary adenomas with an aggressive behavior and a high capacity of invasion and recurrence, aspects that represent an unfavorable prognostic factor