Purpose MicroRNA-21 (miR-21) was reported as being overexpressed in various human cancerous tissues, but its expression in cancerous serum was not unanimous in different laboratories. On the base of optimizing experimental design and improving trial protocol, we wanted to know whether the circulating microRNA-21 was dysregulated in the common solid cancers. Methods Using SYBR green real-time quantitative reverse transcription-PCR, we detected the expression of circulating miR-21 in 174 patients with solid cancers and 39 normal control subjects, including breast cancer, esophageal cancer, gastric cancer, colorectal cancer, lung cancer. Furthermore, we analyzed the associations between miR-21 expression and clinical features of patients. Results miR-21 was significantly overexpressed in human solid cancerous serum relative to normal control ( P  < 0.001), and its sensitivity and specificity were significantly higher than the currently used tumor markers. High miR-21 expression was not correlated with gender, age, clinical stage, and lymph node metastasis status. Conclusion Circulating miR-21 could serve as a potential broad-spectrum serum-based biomarker for the detection of some solid cancers.