The authors studied five patients with primary cutaneous Hodgkin's disease (PCHD). Each patient presented with skin lesions without evidence of systemic HD. Skin lesions were papules or nodules, many of which regressed spontaneously. Lesions were distinguished from lymphomatoid papulosis (LyP) by the presence of numerous diagnostic Reed-Sternberg (RS) cells that expressed CD30 and CD15 but were negative for CD45R; LyP lesions usually are CD15 -, CD45R+. Anaplastic large cell lymphoma (ALCL) was excluded by the polymorphous background of inflammatory cells in PCHD. Three patients with PCHD had a benign course without systemic disease with up to 20 years of follow-up, whereas two other patients developed mixed-cellularity HD in lymph nodes 2 months and 6 years following the onset of PCHD. This study indicates that PCHD does occur as a rare but distinct clinicopathologic entity morphologically and immunophenotypically indistinguishable from nodal HD but with an unexpectedly indolent course in some patients. Patients with PCHD should be observed for development of systemic HD, but unlike patients with LyP or ALCL, an association of PCHD with mycosis fungoides or cutaneous T-cell lymphoma has not yer been observed.