Ulcerative colitis patients have an increased risk of colitis associated cancer (CAC). It is driven by continuous exposure to inflammation and it is different than sporadic colon cancer (CRC). CAC advances through “dysplasia-carcinoma axis” while CRC through “adenoma-carcinoma axis”. In CAC, chronic inflammation exposes the epithelial mucosal defensive lining to inflammatory mediators (cytokines, anti-microbial peptides) causing alteration of microbiota population and immune response. The intercellular receptor Notch1, is critical for stem cell differentiation, lineage commitment, and contributes significantly in carcinogenesis.