Purpose The goals of this study were to report our clinical experience in a single center at a high-volume tertiary university hospital in Istanbul and to introduce a diagnostic algorithm based on a 5-year follow-up of 152 women with biopsy-proven idiopathic granulomatous mastitis (IGM). IGM is an uncommon, non-malignant, chronic inflammatory disease of the mammary gland with an unknown etiology. The symptoms, clinical presentation, and radiologic findings of IGM may resemble carcinomas. To our knowledge, this study comprises the largest series of IGM, especially with a 5-year follow-up, yet reported in the English literature. Methods The present study reported our single-center clinical experience at a tertiary university hospital in Istanbul, Turkey, and introduced a diagnostic algorithm using our treatment protocol based on a 5-year follow-up of 152 women with biopsy-proven IGM. Our database of 10 years' experience containing over 700 patients with IGM was evaluated. However, to assess recurrence and resistance to treatment, only the 152 patients with a long follow-up period of 5 years were included in the study group. The analysis included 152 women with biopsy-proven IGM who were treated between January 2009 and March 2014. The clinical data of the presentation, histopathology, and treatment modalities were analyzed by reviewing the medical records. Results Of the 152 patients diagnosed with granulomatous mastitis, 32 (21%) recovered by expectant management, while 14 (9%) responded to antibiotics, 65 (43%) received corticosteroids, 20 (13%) had antituberculosis medication, 16 (11%) underwent excision, and 5 (3%) responded to non-steroidal anti-inflammatory drugs. Fifty-one patients (33%) had recurrence; of these, 30 achieved a cure with second-line treatment, 16 underwent excision, and 5 achieved a cure with observation. Conclusion IGM is a rare benign breast disorder, and clinicians need a high index of suspicion to diagnose it, as IGM can be mistaken for breast cancer. Unlike periductal mastitis, IGM does not evolve secondary to nicotine addiction and is typically seen in women of childbearing age with a recent history of pregnancy and lactation. The diagnosis can be challenging, and an evaluation with a multidisciplinary team is necessary. There is no consensus concerning the definitive treatment approach. We suggested a diagnostic algorithm in the present study, using our treatment protocol based on the 5 years' follow-up of 152 women.