We report a unique case of indolent lymphoma with an unusual VDJ rearrangement. Polymerase chain reaction (PCR) analysis of bone marrow at the time of diagnosis was positive for both BCL-2/JH and CDRIII rearrangements. After treatment, the patient achieved complete remission (CR) with slow disappearance of both rearrangements (CDRIII and then BCL-2/JH). Subsequently, two new CDRIII rearrangements were detected in bone marrow, peripheral blood, and lymph node tissue. After this conversion, fluorescent activated cell sorting (FACS) analysis demonstrated monoclonal disease, suggesting that both CDRIII rearrangements originated from one cell. Histological evidence of a B-cell small lymphocytic lymphoma (B-SLL) infiltrate in the bone marrow became evident approximately 1 year after the two CDRIII rearrangements appeared. Direct sequencing revealed that one of the CDRIII sequences consisted of a VDVDJ rearrangement. This is the first report of such a rearrangement in a case of indolent lymphoma. This type of rearrangement has been described to result from a secondary VDJ recombination in childhood acute lymphoblastic leukemia (ALL) leading towards oligoclonality and poorer prognosis. Our observations suggest that such a finding in an indolent lymphoma patient may precede transformation into an aggressive disease. Early detection by PCR could have substantial impact on the prognosis of such patients.