Primary lymphoma of bone has characteristic clinical and radiologic manifestations; however, its histologic features and clinical outcome show considerable variability. The histologic and immunophenotypic features of 13 adult patients with lymphoma as a solitary bone lesion were compared with clinical outcome. All tumors studied were non-Hodgkin lymphoma of anaplastic or large cell type and included B-cell (9 cases), T-cell (3 cases), and null cell (1 case) phenotypes. All patients responded well initially to systemic chemotherapy (with or without radiotherapy); however, disease in 6 patients progressed or recurred, and 5 patients died of disease. Local disease progression was seen in 2 patients, with 4 patients experiencing relapse at distant sites. Expression of CD30, present in 7 cases, was associated with an anaplastic or large noncleaved histologic appearance. Absence of CD30 expression characterized 6 cases, including 4 with multilobate or cleaved morphologic features. Five of 6 cases that recurred were associated with CD30 expression, including 3 with anaplastic features. The 4 tumors with cleaved or multilobate nuclear morphologic features were associated with long disease-free survivals and may represent a distinct lymphoma subtype with a good prognosis.