Reticulohistiocytoma and multicentric reticulohistiocytosis are designations for uncommon, incompletely characterized histiocytic proliferations of the skin or soft tissues. In this study, we analyzed a uniform group of 44 lesions composed of epithelioid histiocytes, comprising a subset of lesions originally designated as reticulohistiocytoma, and propose designating them as "solitary epithelioid histiocytoma" (SEH), in line with the recently published classification proposal for histiocytic disorders. There were 26 males and 18 females with a median age of 35 years (range, 2.5-74 years). All patients had a superficial, circumscribed, mildly elevated, solitary lesion (size range, 1.5-11 mm; median, 4 mm), located in the trunk wall (n = 16), lower extremity (n = 12), head and neck (n = 8, including 2 in the oral cavity), upper extremity (n = 6), penis (n = 1), and an unspecified site (n = 1). Histologically, the lesions typically involved upper and mid-dermis and were not ulcerated. They were composed of large epithelioid histiocytes with a varying number of lymphocytes and neutrophils. The histiocytes had abundant, typically densely eosinophilic, cytoplasm and mostly mild, if any, nuclear atypia. Multinucleated forms with randomly oriented nuclei were also present. The histiocytes had low mitotic activity (range, 0-4 mitoses per 10 wide HPFs; median, 1 mitosis per 10 HPFs). The lesions contained varying numbers of CD3-positive T cells, whereas B lymphocytes, plasma cells, eosinophils, and mast cells were scant, if present at all. Immunohistochemically, the epithelioid histiocytes were positive for CD163, CD68, lysozyme (variably), and vimentin. They often had focal nuclear immunoreactivity for microphthalmia transcription factor, and they sometimes had focal reactivity for Factor XIIIa and S-100 protein. Membrane positivity for CD31, CD43, and CD45 was variable. The epithelioid histiocytes were consistently negative for CD3, CD20, CD30, HMB45, and keratins. All 12 patients with follow-up information had an uneventful clinical course with no recurrences (median, 13 years). SEH is a benign, probably reactive, histiocytic proliferation of unknown etiology. It needs to be distinguished from Rosai-Dorfman disease, juvenile xanthogranuloma, a variety of granulomatous conditions, and some malignant neoplasms, including histiocytic sarcoma, melanoma, and epithelioid sarcoma.