Primary cutaneous B-cell lymphomas (pCBCLs) represent a distinctive group from both the clinical and histomorphologic point of view, and, when compared with node-based lymphomas, tend to have a much more indolent behavior. In light of current knowledge of Skin Immune System (SIS), the actual cutaneous origin of pCBCLs and their relationship to SIS are an interesting matter of debate. In 24 cases of pCBCLs, we evaluated the evolutionary modifications of reactive T-cell infiltrate and the morphologic evidence of High Endothelial Venules (HEV). The amount of reactive T-cells was inversely related to the growth rate of skin lesions; a significant correlation was found between amount of reactive T-cells and HEV expression. Interestingly, the dramatic reduction of reactive T-cells and rapid growth of neoplastic B-cells found in nodular, quickly growing lesions, does not however correlate with the quite good overall clinico-biologic behavior of pCBCLs.