Bcl-2 family protein plays an important role in apoptosis and its overexpression is protects neoplastic cell from apoptotic stimuli. Cutaneous B-cell lymphoma are rare non-Hodgkin lymphomas and can be classified in primary forms, featuring an exclusive skin-involvement at diagnosis, and cutaneous spread of a nodal disease. Such a distinction is not trivial, owing to different prognosis (indolent vs. aggressive) and therapeutic management. Bcl-2 expression at immunohistochemistry can be crucial in differential diagnosis between cutaneous and systemic disease, as well as between the different primary cutaneous forms. In the last few years, an animated debate on the prognostic role of Bcl-2 overexpression at molecular analysis have been developed in cutaneous B-cell lymphoma. To conclude, Bcl-2 expression have a diagnostic role more than prognostic in primary cutaneous B-cell lymphomas.