From a series of 75 cases of mixed spindle cell and epithelioid cell nevi, 14 were designated as desmoplastic nevi. Junctional activity, theque formation, and pigmentation were uncommon features. As a result, desmoplastic nevi may be confused with a variety of fibrohistiocytic lesions. Well defined intranuclear invaginations of cytoplasm occurred in 12 cases, and were helpful in differentiating desmoplastic nevi from these lesions. Desmoplastic malignant melanoma must also be considered in the microscopic differential diagnosis, but distinguishing features of desmoplastic melanoma include the presence of preexisting lentiginous melanoma, and necrosis of tumor cells and collagen. Desmoplastic nevus was compared to the ordinary variants of mixed spindle cell and eipthelioid cell nevus in an attempt to define etiologic factors responsible for a desmoplastic reaction. No satisfactory explanation could be found since the clinical variables examined were not statistically different.