A 70-year-old Italian man with a history of squamous cell carcinoma of the lung presented with a nodular skin eruption. He had traveled extensively in India and Sri Lanka. The nodules were well demarcated and measured up to 3.5 cm in diameter. Histologically, there was a proliferation of spindled and polygonal cells with focal and relatively inconspicuous cytoplasmic vacuolation. A macrophage-monocyte lineage for the cells was confirmed by paraffin section immunohistochemistry, using the monoclonal antibodies anti-CD45, MAC-387, KP-1, UCHL-1, MT-1, L26, and MB2. Infiltrating borders, extension of the lesion into the subcutis, and involvement of small dermal nerves and eccrine glands initially suggested the possibility of a "histiocytic" neoplasm of indeterminate biological potential. However, air-dried and Giemsa-stained material from a fine-needle aspirate of one cutaneous nodule showed needle-shaped intracellular "negative images," and acid-fast stains revealed a large number of intracytoplasmic bacilli in virtually all of the vacuolated lesional cells. Furthermore, a second skin nodule that was excised 3 weeks after initial presentation showed the typical morphology of lepromatous leprosy. The clinicopathologic features of this case demonstrated several similarities with those of so-called "histoid" leprosy. Unusual morphologic variants of leprosy need to be considered in the interpretation of unusual "histiocytic" infiltrates in order to avoid a mistaken diagnosis of neoplasia, regardless of the geographic locale in which the patient is evaluated.