– Persistent polyclonal B-cell lymphocytosis (PPBL) is a rare entity of unknown origin usually observed in smoking women, characterized by binucleated B-lymphocytes and a specific clinical course. We described a case of an “atypical” form of PPBL in a no smoking woman suffering from bone marrow involvement by breast cancer cells with concomitant circulating polyclonal B-lymphocytes without augmenting in serum polyclonal IgM levels. No cytogenetic abnormalities were found. To date, it is not clear whether a PPBL may represent a response to a bone marrow involvement of breast cancer or a pre-neoplastic reality, preceding the emergence of a predominant clone. Recently, because of the natural history of PPBL remain unclear and unclassifiable in the current hematological malignancies, these patients need to undertake a careful long-term follow-up.