Heat shock proteins (hsp) are molecular chaperones that are increased by various environmental and patho-physiological stimuli. Hsp can bind to mutant/wild-type p53 in tumors and, consequently, could not only regulate p53 accumulation or localization but also modulate its biological effects on cells. However, there is little information available on the significance of hsp expression in colorectal cancer. The aim of our study was to investigate the relationship of hsp to p53 expression, clinico-pathological factors and prognosis in a series of 256 patients with colorectal adenocarcinomas, using immuno-histochemistry. Seventy-five cases exhibited hsp expression in the cytoplasm, with 11 presenting both cytoplasmic and nuclear staining. Hsp expression was related positively to cytoplasmic p53 expression but not to nuclear p53 expression. In the subgroup of rectal tumors, hsp over-expression appeared to predict unfavorable survival, though its prognostic value diminished using multivariate analysis. There were no significant relationships of hsp with patient sex or age, tumor site, Duke's stage, growth pattern or differentiation.