Colorectal cancer (CRC) is among the most common malignancies and remains a major cause of cancer-related death worldwide. Despite recent advances in surgical and multimodal therapies, the overall survival of advanced CRC patients remains very low. Cancer progression, including invasion and metastasis, is a major cause of death among CRC patients. The underlying mechanisms of action resulting in cancer progression are beginning to unravel. The reported molecular and biochemical mechanisms that might contribute to the phenotypic changes in favor of carcinogenesis include apoptosis inhibition, enhanced tumor cell proliferation, increased invasiveness, cell adhesion perturbations, angiogenesis promotion, and immune surveillance inhibition. These events may contribute to the development and progression of cancer. A biomarker is a molecule that can be detected in tissue, blood, or stool samples to allow the identification of pathological conditions such as cancer. Thus, it would be beneficial to identify reliable and practical molecular biomarkers that aid in the diagnostic and therapeutic processes of CRC. Recent research has targeted the development of biomarkers that aid in the early diagnosis and prognostic stratification of CRC. Despite that, the identification of diagnostic, prognostic, and/or predictive biomarkers remains challenging, and previously identified biomarkers might be insufficient to be clinically applicable or offer high patient acceptability. Here, we discuss recent advances in the development of molecular biomarkers for their potential usefulness in early and less-invasive diagnosis, treatment, and follow-up of CRC.