In a patient affected by acute lymphoblastic leukemia (ALL) and subjected to therapy with Erwinia L-asparaginase, acute parotitis was observed. Microbiological studies excluded any infectious etiology. Regression of parotitis was spontaneous. This complication has not been previously reported and could be due to the same mechanism of pancreatic injury. The occurrence of acute parotitis needs to be promptly recognized in order to avoid the continuation of L-asparaginase.