Prostate-specific antigen (PSA) decline after discontinuation of estramustine phosphate (EMP) is extremely rare. We report a case with dramatic PSA decline after withdrawal of EMP. A patient with prostate cancer had been treated with luteinizing hormone-releasing hormone and EMP. After refractory, EMP was withdrawn. After withdrawal of EMP, PSA dramatically decreased from 214 ng/mL to 3.71 ng/mL (98.5% decline) and remained low for more than 17 months. In association with PSA decline, lumbago and metastatic lesions improved. We should be aware of this phenomenon and the discontinuation of EMP is recommended in patients with rising PSA after an initial response to EMP.