We studied two cases of pigmented neuroectodermal tumor of infancy (PNTI) by routine light microscopy and immunohistochemistry on formalin fixed, paraffin embedded tissues using antibodies to HMB‐45 “melanoma associated” antigen, S‐100 protein, neuron specific enolase (NSE), Leu‐7 antigen, chromogranin, epithelial membrane antigen, collagen Type IV, alpha‐fetoprotein and muscle‐specific actin and to the intermediate filaments cytokeratin (CK), vimentin, desmin and neural filaments. We found that the large epithelioid cells, many of which contained melanin pigment, were strongly positive for CK and HMB‐45, and less intensively positive for vimentin and NSE. The small neuroblast‐like cells revealed only focal, weak NSE positivity. Both cell types were negative for S‐100 protein and for the other antigens examined. Our results suggest that: (1) the large and small cell populations in PNTI have different immunophenotypes; (2) the expression of CK and HMB‐45, together with the S‐100 negativity, appears unique for the pigmented cells; and (3) this profile may be helpful in the exclusion of melanoma and peripheral neuroblastoma from the differential diagnosis.Argenyi ZB, Schelper RL, Balogh K. Pigmented neuroectodermal tumor of infancy. A light microscopic and im