We have investigated the expression and role of the 58-kDa microspherule protein (MSP58) in colorectal carcinoma (CRC). By immuhistochemistry and immunofluorescence, we observed MSP58 in the nucleus and cytoplasm of CRC cells, and found MSP58 to be present in CRC specimens more often than in adjacent non-tumor tissues (92.5 vs 36.3%, P < 0.01). The average staining score in adjacent non-tumor tissues was significantly lower than in CRC tissues (2.05 +/- 1.13 vs 5.23 +/- 1.38, P < 0.01). Moreover, MSP58 mRNA and protein appeared to be upregulated in six fresh CRC samples compared to their adjacent non-cancerous tissues. MSP58 expression was also detected in the human CRC-derived cell lines LoVo, CoLo205, HCT116, HT-29, SW620, and SW480. Downregulation of MSP58 inhibited in vitro growth and attenuated tumor growth in animal models by induction of cell cycle arrest, and was associated with reduced levels of cyclin D1, cyclin-dependent kinase 4, phosphorylation-Rb (p-Rb), p21, and Retino blastoma (Rb) proteins. These results indicated that MSP58 might play an important role in the carcinogenesis of CRC via regulation of the cyclin D1-cyclin-dependent kinase 4-p21 pathway.