Objective: To investigate the efficiency of pingyangmycin (PYM) intralesional injection for the treatment of ranulas in clinical practice. Methods: PYM concentrations were 2.0 mg/ml (8 mg PYM powder + 1 ml normal saline + 2 ml 2% lidocaine + 1 ml dexamethasone). The mixed PYM solution was intralesional injected into ranulas after drawing out isometric cyst fluid in 3 patients. Results: The ranulas of 3 patients showed total disappearance after the sclerotherapy, and no recurrence was found after 6 months to 3 years’ follow-up. Compared to surgical therapy, the PYM sclerotherapy was advocated by clinicians for its advantages of less injury, no scar, less suffering, etc. Conclusions: PYM is an effective sclerosing agent for ranulas. Intracystic injection of PYM may be an optimal method for the treatment of ranulas.