We report a 43-year-old woman with sebaceous gland hyperplasia that occurred in a diffuse pattern of aggregated papular lesions involving her entire face, neck, and upper chest. Comedones, pustules, and inflammatory papules were absent. The eruption was accompanied by marked seborrhea. Histopathological examination showed enlargement of sebaceous acini, an increased number of immature sebocytes in foci, and a dilated follicular infundibulum. Immunohistochemical investigation showed cytokeratin 14 (CK 14) expression in the keratinocytes of the infundibulum, the isthmus, and sebaceous duct and in the mature and immature sebocytes; CK 17 expression in the keratinocytes of the sebaceous duct; CK 1 expression in the keratinocytes of the infundibulum; and an enhanced expression of the proliferation cell antigen Ki-67 (MiB1) in the immature sebocytes. With CK 18 and CK 19, no staining was observed. Oral therapy with isotretinoin (13-cis-retinoic acid) resulted in remarkable improvement in < or = 3 months. Histopathological and immunohistochemical examination after therapy showed markedly reduced sebaceous glands, a decrease in the staining of MiB1-positive immature sebocytes, and enhanced expression of CK 19 in immature sebocytes and sebaceous duct cells. Diffuse sebaceous gland hyperplasia is a rare variant of seboglandular proliferative disorders that is distinct from the well-known circumscribed type.