Our group has previously demonstrated that expression of the cytokine stem cell factor (SCF) by leukemic blasts is a frequent finding in pre-B acute lymphoblastic leukemia (ALL). Whether SCF expression is a feature of other B cell malignancies and whether cross-talk from the local microenvironment modulates malignant cell SCF production are, however, unknown. Here we show using immunohistochemistry that SCF is expressed by a wide variety of indolent and aggressive B cell malignancies involving the bone marrow (BM) or lymph nodes (LNs). In diseases such as follicular lymphoma (FL), however, where lymphoma cells uniquely associate with the BM endosteal niche, BM lymphoma does not express SCF, while LN involvement is SCF positive. In contrast, cases of FL with high-grade transformation in the BM are SCF positive. These data suggest that lymphoma cell interaction with the endosteal niche inhibits SCF production, and that FL cells become independent of this microenvironment effect following transformation.