Advanced extramammary Paget's disease (EMPD) is a rare skin cancer with no standard treatment. Anti-programmed cell death protein 1 (PD-1) agents are indicated for the treatment of EMPD with high tumor mutation burden (TMB) in Japan, but neither drug is necessarily effective. This report describes an 83-year-old male patient who presented with a macerated, reddish, 3-cm tumor on the umbilicus. Three years later, he developed metastasis of lymph nodes in the left inguinal region. He was diagnosed with EMPD. Positron emission tomography-computed tomography (PET-CT) revealed metastases to the lung and the bone. S-1 plus docetaxel therapy was begun, but the metastatic lesions were increased. A gene panel testing indicated a high TMB, so pembrolizumab was begun. After the second administration, Grade 3 acute kidney injury developed due to immune checkpoint inhibitors (ICIs). The treatment was discontinued after two administrations due to immune-related adverse events. All the metastases disappeared in seven months after the start of pembrolizumab administration. As far as we know, the present patient is the first case of advanced EMPD with a complete response to ICI. The efficacy of ICIs against EMPD awaits future investigation enrolling a larger patient cohort.