When monoclonal gammopathies arise in persons without evidence of plasma cell malignancy or lymphoproliferative disease, the term 'monoclonal gammopathy of unknown significance' (MGUS) can be used. MGUS is believed to be the preneoplastic phase of lymphoproliferative diseases because many of these patients eventually develop malignant disease, mainly multiple myeloma. We have previously identified human papillomavirus (HPV) in a chronic benign plasma cell tumor of the cervix and in the bone marrow of multiple-myeloma patients. In the following study, we expanded upon our initial observation by analyzing 14 patients with MGUS. Bone marrow biopsies of the patients were analyzed for HPV sequences using polymerase chain reaction (PCR) and in situ hybridization. Normal controls included 26 bone marrow specimens, 24 analyzed by PCR and two by in situ hybridization. A significant association was found to exist between HPV and MGUS (p = 0.001). Among 14 patients with MGUS, HPV sequences have been identified in 10 of the bone marrow biopsies. These results suggest that HPV can reside in the bone marrow of a premalignant lymphoproliferative disease. Copyright 1996 S. Karger AG, Basel