Ber-EP4 is an antibody raised against a cell membrane glycoprotein of, as yet, unknown function. In the skin, the ability to distinguish basal cell carcinoma from squamous cell carcinoma has been emphasized. Immunoreactivity in apocrine and eccrine secretory coil epithelium, Merkel cell carcinoma, and cutaneous mixed tumor has been reported. Having observed more widespread staining than previously reported, we sought to characterize further Ber-EP4 immunoreactivity by examining 76 formalin-fixed and paraffin-embedded proliferative epithelial skin lesions, 2 sections of fetal skin with developing adnexa, and frozen sections of skin from Mohs surgery procedures, using hematoxylin and eosin and Ber-EP4 immunostaining. In paraffin-embedded skin, matrical and outer sheath epithelium of vellus anagen follicles, inferior segment epithelium of vellus telogen follicles, and secretory coils of sweat glands stain with Ber-EP4, but anagen terminal follicle epithelium and eccrine and apocrine sweat ducts are negative. On frozen section, additional staining of eccrine ducts and cells in the outer sheath and matrix of the inferior segment of terminal follicles is noted. Basaloid epithelium of trichoepitheliomas, follicular induction over dermatofibromas, mammary Paget's disease, and selected other neoplasms showing eccrine or apocrine differentiation stain with Ber-EP4. These data indicate that in addition to basal cell carcinoma, Ber-EP4 staining may be seen in a variety of proliferative epidermal and adnexal lesions.