Background: The release of microvesicles (MVs) is an essential phenomenon for inter-cellular signaling in health and disease. The role of MVs in cancer is multidimensional and includes cancer cell survival, proliferation, and invasion. In this prospective study, we analyzed MV levels in colorectal cancer patients and assessed the importance of MV release in early-stage colorectal cancer and survival. Methods: This study included 98 patients and 15 controls. The characterization of MVs from human plasma was performed by flow cytometry using monoclonal antibodies. Results: The levels of total MVs and MUC-1-positive, tissue factor (TF)-positive, and endothelial cell-derived MVs (EMVs) were statistically significantly higher in the colon cancer patients than in the controls (p < 0.001). Furthermore, the subgroup of patients with very early-stage colorectal cancer also had statistically significant differences in the levels of the abovementioned MVs compared to the controls (p < 0.01). Highly differentiated tumors had lower levels of MUC-1-positive MVs (p < 0.02), EMVs (p < 0.002), and EMV/TF combinations (p < 0.001) versus those with tumors with low/intermediate differentiation. Conclusions: Our data demonstrate that the analysis of circulating MV levels in plasma could possibly become a tool for the early diagnosis of colon cancer at a very early stage of the disease.