The aim of the study was to investigate the expression of PGP 9.5 in cutaneous keratoacanthomas (KAs) and squamous cell carcinomas (SCCs). Thirty-one cases of KA (10 in the growth stage, 9 in the mature phase and 12 in the involution stage) and 36 SCCs including 13 well differentiated cases, 12 moderately differentiated tumors, 7 poorly differentiated lesions and 4 pseudoadenoid entities were investigated. PGP 9.5 expression was positively correlated with tumor stage (P < 0.001) and potential perineural invasion (P < 0.001). There was no significant difference in the distribution of patients presenting variable levels of PGP 9.5 staining with regard to maximal tumor size and the extent and degree of stromal invasion. PGP 9.5 expression proved closely associated with tumor aggressiveness and is classified as a marker for predicting the outcome of resection-treated skin cancer patients.