Twenty patients with non-Hodgkin's lymphoma (NHL) had different histologic subtypes of NHL in multiple sites or in a single tumor mass either at the time of their initial biopsy and staging (13 patients) or in the course of their disease (seven patients). These 20 cases represent 3.7% of all patients with NHL seen at the University of Chicago between January 1968 and May 1979. The five-year actuarial survival rate for all 20 patients was 68%. For those 13 patients who had multiple histologic subtypes at the initial workup, the five-year survival rate was 45%; for the seven patients who developed a new histologic subtype later in the course of the disease, the five-year survival rate was 85%. In the latter group of patients, however, the initial biopsy specimens demonstrated better prognostic subtypes, and the median survival from the time of diagnosis of a new, less favorable histologic subtype averaged only four months. These findings indicate that the prognosis is related to the least favorable histologic subtype present, unless this is only a minor component of a composite lymphoma or is limited to one extranodal site.