An otherwise healthy 50-year-old woman presented with a 6-month history of having developed more than 100 generalized, non-confluent, reddish-brown, partially yellow-coloured papules. A non-epidemotropic, monomorphous infiltrate of vacuolated mononuclear, and occasionally multinuclear, histiocytes, positive for factor XIIIa and macrophage markers HAM56 and KiM1p, was consistent with the clinical impression of generalized eruptive histiocytomas. However, the additional reactivity for S100 protein, in the absence of features of histiocytosis X, suggested a diagnosis of indeterminate cell histiocytosis (ICH). Further immunohistochemical studies, performed on snap-frozen material, characterized the lesions as being diffusely positive with LN3 (HLA-DR), Leu4 (CD3) and Leu3 (CD4), the infiltrate in the upper dermis as reactive for OKT6 (CD1) and IOT6c (CD1c), and the infiltrate in the lower dermis as reactive for a variety of macrophage markers. Ultrastructural studies showed various non-specific features of histocytic disorders, but no Birbeck granules. Our findings confirm those of previous reports suggesting that ICH is a distinct histiocytic entity, characterized by immunophenotypic features of both X- and non-X histiocytoses. Generalized eruptive histiocytoma seems to be an early indeterminate stage of various non-X histiocytic syndromes including ICH, multicentric reticulohistiocytosis, xanthogranuloma and xanthoma disseminatum. The distribution pattern of the various X/non-X histiocytic markers suggests dermal arrest of antigen-presenting cells during their physiological trafficking from the skin to the lymph nodes.