The authors have recently proposed to use the name pachyonychia as an umbrella term that includes 2 distinctly different entities in the form of congenital pachyonychia and acquired longitudinal pachyonychia. Congenital pachyonychia is defined by a diffuse hyperkeratosis of the nail bed. Acquired longitudinal pachyonychia correspond to the true definition of pachyonychia, that is, a thickened nail plate without subungual keratosis. Acquired (monodactylous) pachyonychia can be diffuse typifying onychomatricoma or localized as a longitudinal band with three etiological possibilities: onychomatricoma, onychocytic matricoma, and onychocytic carcinoma. On histopathological examination, onychomatricoma is a fibroepithelial tumor; conversely, onychocytic matricoma and carcinoma are purely epithelial tumors. The purpose of this study was to present the clinical, pathological, and immunohistochemical profiles of 2 cases of in situ onychocytic carcinoma, to discuss the role of high-risk human papillomavirus in the pathogenesis of this tumor, and to confirm the interest value of nail clipping microscopy in the surgical planning of the acquired (monodactylous) pachyonychia band pattern. Two men were referred for a longitudinal thickening of the lateral part of the nail plate of their fingers. The bands were yellowish with a faint to dominant black coloration. Nail clippings were obtained before excision in one case; the nail plate was thickened with minute holes in a honeycomb pattern. Nail biopsy specimens revealed an onychocytic carcinoma with epithelial projections inducing active production of the nail plate and multiple minute cavitations into the thick nail plate. Hair-related keratins were expressed in all specimens. One tumor expressed p16 in a diffuse pattern, whereas the other showed an unspecific faint patchy staining. p53 was negative. A clinical finding of longitudinal pachyonychia, which by nail clipping microscopy contains small cavities in a honeycomb-like pattern, should be considered an alert to the possibility of a malignant lesions.