Loss of SATB2 expression has emerged as a promising biomarker for dysplasia in inflammatory bowel disease (IBD), but its sensitivity and specificity remain unclear. We retrospectively evaluated immunohistochemical (IHC) staining of SATB2 and p53 in colorectal biopsies from 37 IBD patients (25 men and 12 women; median age: 48 years) with suspected dysplasia. The cohort included 26 ulcerative colitis (70%) and 11 Crohn's disease (30%). Fourteen patients (38%) developed IBD-associated invasive carcinoma, and 18 (49%) had persistent dysplasia on follow-up. Histologic review identified 80 lesions initially diagnosed as negative (16%), indefinite (39%), low-grade (36%), and high-grade (9%) dysplasia. IHC revealed aberrant p53 in 35 lesions (44%) and SATB2 loss in 42 lesions (53%), with 19 (24%) showing both abnormalities. Reappraisal of diagnoses combining histology and IHC reclassified lesions into indefinite (20%), low-grade (63%), and high-grade (17%) dysplasia. Lesions with SATB2 loss alone were more frequently of lower grade (P = .003). Dysplasia types included 15 conventional dysplasia (19%) and 65 nonconventional dysplasia (81%). The rates of p53 abnormality, SATB2 loss, and their combination were similar in nonconventional dysplasia (45%, 55%, and 75%, respectively) and conventional dysplasia (40%, 47%, and 67%, respectively) and comparable between cancer patients (50%, 56%, and 74%, respectively) and noncancer patients (39%, 50%, and 72%, respectively). Missed dysplasias in cancer patients were all nonconventional, and lesions with p53 abnormality more likely progressed to cancer (P = .002). In conclusion, SATB2 loss is a sensitive marker for IBD-associated dysplasia. Combined use of SATB2 and p53 IHC improves dysplasia detection and reduces false-negative diagnosis, supporting its application into routine diagnostic practice.