In 22 histologic cases of subcutaneous panniculitis-like lymphoma, we studied the clinicopathologic differences between CD56- and CD56+ cases (11 each). CD56- cases had skin ulcers (1 [9%]); tumor invasion in the superficial dermis (1 [9%]); erythrophagocytosis (10 [91%]); and medium-sized (11 [100%]), CD8+ (10 [91%]), T-cell receptor (TcR)betaF1+ (10 [91%]), and CD95 (Fas)- tumor cells. CD56+ cases had skin ulcers (9 [82%]); tumor invasion in the superficial dermis (8 [73%]); erythrophagocytosis (1 [9%]); and pleomorphic large (10 [91%]), CD8+ (2/10 [20%]), TcRbetaF1 + (3/10 [30%]), and CD95 (Fas)+ (7/10 [70%]) tumor cells. These 7 factors were significantly different between groups (P < .01). Median survival rates were 96 and 12 months for the CD56- and CD56+ groups, respectively. Age younger than 40 years, no skin ulcers, no tumor invasion in the superficial dermis, and CD8+, TcRbetaF1 +, CD95 (Fas)-, and CD56- tumor cells were significantly better prognostic factors (P < .01). The CD56- and CD56+ groups showed different tumor cell characteristics, clinicopathologic findings, and prognosis. In the CD56+ group, 1 was gamma/delta T-cell phenotype, 3 were alpha/beta T-cell, and 6 were TcRbetaF1- and gamma/delta- NK/T-cell, and 3 NK/T-cell cases had nuclear signals of Epstein-Barr virus-encoded RNA. Cases of CD56+ T- and NK/T-cell lymphoma had similar clinicopathologic findings and prognosis.