Bruton's tyrosine kinase (BTK), a Tec family non-receptor tyrosine kinase that is required for B cell development, is critical for the initiation and maintenance of human B-cell malignancies. However, the expression of BTK and the role that BTK plays in the pathogenesis of multiple myeloma (MM) remain seldom reported. In this study we examined the expression and screened for gene mutations of BTK in MM cells. We showed that BTK was elevated and activated in a dexamethasone-resistant cell line and in two out of nine (22.2%) patients' cells. Interestingly, patients with higher BTK expression had a poorer prognosis. In addition, a single nucleotide polymorphism (SNP) at cDNA position 2062 (T2062C) in the BTK gene was recorded in six out of eight (75%) patients and in U266 cells. This SNP in MM cells was not detected in other malignant hematopoietic cells of different lineages. These results suggest that the function of BTK warrants further investigation, and BTK expression might be used as a prognostic indicator for patients with MM.