Background: The incidence of pancreatic adenocarcinoma (PDAC) in patients with chronic pancreatitis (CP) is as high as 5%. It is a commonly encountered diagnostic challenge in patients with CP on long-term follow-up. Summary: This review consolidates the existing literature on assessment of PDAC in background of CP, its evaluation through the available investigations, surgical management, and prognostication. Recent change in symptomatology of an otherwise stable CP should raise a suspicion of malignancy. Endoscopic ultrasound (EUS) is more specific and sensitive in establishing the diagnosis of PDAC compared to cross-sectional imaging (computed tomography/magnetic resonance imaging). Intraoperative assessment with careful palpation coupled with careful clinical judgment helps in differentiating between an inflammatory mass and pancreatic cancer. Confirmation can be obtained with either preoperative EUS-guided fine needle cytology/core biopsy or intraoperative core biopsy under ultrasound guidance. However, despite complete evaluation with above options, 1–6% patients often show malignancy on final histopathological examination. Key Messages: Diagnosis of PDAC in CP needs a high index of suspicion. Cross-sectional imaging has poor negative predictive value. CA 19-9 with MUC5AC combination may become an ideal investigation. EUS with core biopsy/frozen section has a good sensitivity and specificity and low false negative results. Complete radical resection should be the aim to get long-term survival.