Calcium-binding tyrosine phosphorylation regulated protein (CABYR), a family of isoforms resulting from alternative splicing, has been identified as a cancer/testis antigen (CT88) in lung cancer and hypothesized to be a promising target for immunotherapy. Here, we report the expression of CABYR in various cancer tissues/cell lines. Expression profiles of individual isoforms were different among cancers. Furthermore, protein and mRNA levels did not correlate for individual isoforms. While CABYR-c/d were the most abundant splicing variants, CABYR-a was the predominant protein isoform. Finally, CABYR-a, but not CABYR-c, was found to interact with α-enolase in vivo. Collectively, the data indicate that CABYR is a CT antigen widely expressed in diverse cancer cells. However, individual protein isoforms may be differentially regulated by post-transcriptional and post-translational mechanisms and may have a unique role in carcinogenesis. The protein expression pattern of various CABYR isoforms is important with regard to the consideration of using CABYR as a target antigen for the development of vaccines for cancer therapy.