The diagnosis ofin situfollicular lymphoma (FL) is feasible when immunohistochemical characterization is carried out and genetic abnormalities are assessed. We usually use a selected diagnostic panel of antibodies (CD10, CD20, CD23, BCL2, BCL6, and Ki67) in lymph nodes with follicular hyperplasia only when we analyze an unexplained lymphadenopathy. Molecular studies, for example, fluorescencein situhybridization analysis for t(14;18), are restricted to doubtful cases in which immunohistochemistry data are ambiguous. Immunohistochemically, the involved follicles show strongly positive staining for BCL2 and CD10. The BCL2+ cells are confined only to germinal centers and are not seen in the interfollicular region or elsewhere in the lymph node. The BCL2 staining in the abnormal follicles is notable for its high-level and uniform intensity.In situFL may be associated with overt FL or with lymphomas other than FL or with other malignancies. The crucial point relies on distinguishingin situFL arising in asymptomatic patients from cases with presence of lymphoma at the same or other sites. Other open questions remain on the frequency with whichin situFLs occur and the frequency of concomitant systemic disease.