We report two cases of adrenal insufficiency (AI) occurring during neoadjuvant treatment with pembrolizumab for breast cancer. In the first case, a 53-year-old female presented with a chief complaint of poor oral intake and fatigue. In the second case, a 46-year-old female presented with a chief complaint of fever, poor oral intake, and general fatigue and was admitted with a diagnosis of pneumonia. Her symptoms did not improve during treatment for pneumonia. After that, two patients were diagnosed with pembrolizumab-induced adrenal insufficiency and were treated with hydrocortisone with improvement in their symptoms. AI due to pembrolizumab use is a relatively rare adverse event, but if it is detected late, it can be potentially life-threatening. In both cases, there were clear changes in the common terminology criteria for adverse events (CTCAE) grade at the time of diagnosis of AI. It may be useful for early detection of AI. The CTCAE version 5.0 was used to assess the severity of adverse events.