Since primary lymphoma of bone (PLB) exhibits morphologic diversity and variability in individual survival, we analyzed the relationship between histopathologic features and biological behavior in 33 patients treated at the Massachusetts General Hospital. Three major histologic subgroups were identified, based on a variety of criteria, the most important of which were the predominance of cells with or without nuclear clefts and the degree of pleomorphism. The probability of NED survival at five years was 64% for patients with tumor predominantly composed of cleaved cells, 13% for those with tumors classified in the noncleaved cell tumor group, and 0% (no survivors) for the pleomorphic subgroup. When tumors were subclassified according to the size of the predominant cell (small versus large), this parameter was found to be of no value in preceding NED survival. Factors that could have potentially influenced the results were analyzed. Since this is a retrospective review, the questions addressed in this study should be further studied in a prospective way.