Asynchronous replication of homologous loci was reported in lymphocytes of patients with lymphoma, ovarian and renal cancer as well as in lymphocytes of patients with premalignant conditions, for example, essential mixed cryoglobulinemia associated with hepatitis C virus and in monoclonal gammopathy of unknown significance. In the present study we evaluated the replication pattern in lymphocytes of four groups of patients with intermediate grade of non-Hodgkin lymphoma at various stages of their disease: 1) at diagnosis; 2) during cytotoxic treatment; 3) in remission; and 4) in relapse. A significantly higher proportion of the asynchronous pattern of replication at diagnosis, during cytotoxic treatment, and in relapse was noted as compared to healthy controls and to patients who achieved remission of their lymphoma. Also, the frequency of the two doublets (DD) pattern in every group studied was significantly lower than in the controls. If our findings can be confirmed in larger, long-term prospective studies, it may allow the use of a simple and inexpensive tool to closely observe patients with lymphoma who are at high risk for relapse.