BACKGROUND: Although often overlooked, drug-induced pancreatitis is a frequent cause of pancreatitis. Pancreatic drug toxicity is defined according to the classification by Mallory et al. and Trivedi et al. Isotretinoin is only classified as possibly toxic to the pancreas (class 3). We report the first case of recurrence of pancreatitis after rechallenge, which argues for a modification of the classification of drug-induced pancreatitis. CASE PRESENTATION: We present here the case of a 20-year-old Belgian man who suffered several episodes of acute pancreatitis for which no etiology could be identified despite an exhaustive assessment. Eventually, as a precaution, isotretinoin was discontinued and there was no recurrence until it was reintroduced. CONCLUSION: This is the 25th case described in the literature, but the first with a positive rechallenge on two occasions. This case therefore implies that isotretinoin should definitely be considered a class 1 toxic drug for the pancreas and should be incriminated in acute pancreatitis in patients treated with this drug.