Acute necrotic pancreatitis was diagnosed in two patients treated with asparaginase for, in the first case a highly malignant lymphoma and in the second an acute lymphoblastic leukemia. The diagnosis on clinical findings and amylase assay results was confirmed by LDH and/or C reactive protein values and abdominal CT scans. Both patients recovered after drainage of peripancreatic fluid collections, in the first patient by surgical followed by cutaneous drainage and in the second by cutaneous drainage of a pancreatic pseudocyst. In addition to the frequent pancreatic reaction observed during asparaginase treatment, signs of pancreatic necrosis requiring urgent treatment have to be identified. The necrotic nature of the pancreatitis was confirmed by clinical examination, assay to biologic markers and abdominal CT scans, eliminating other causes of the pancreatitis.