To evaluate nuclear factor-κB (NF-κB) activity in primary myeloma cells from myeloma patients, we confirmed that the expression levels of CD54 showed a good correlation with the levels of DNA binding activity for NF-κB in human myeloma cell lines, and thus analyzed the expression levels of CD54 on CD38(++) plasma cell fractions as one of NF-κB activity. Primary myeloma cells unexpectedly showed constitutively lower expressions of CD54 than normal bone marrow (BM) plasma cells. Furthermore, the expression levels of CD54 on these plasma cells showed a significant correlation with the plasma levels of CXCL12 stromal cell-derived factor-1a (SDF-1a) in their BM aspirates, and the expressions of CXCR4, the receptor for CXCL12, decreased on primary myeloma cells compared with normal BM plasma cells. It was also confirmed that the addition of CXCL12 to the in vitro culture significantly induced the up-regulation of CD54 expression in primary myeloma cells. In addition, myeloma cells with lower expressions of CD54 were more unstable in the in vitro culture, resulting in a marked reduction of the viable cell number. In the immunohistochemical analysis of BM aspirates, myeloma cells with lower CD54 expression resided in the perivascular regions. Therefore, these data suggest that primary myeloma cells exhibit constitutively lower CD54 that might be partially regulated by CXCL12, and their localizations in the BM may be associated with the expression levels of CD54.