Introduction: Painful bladder syndrome (PBS) is a bladder syndrome of unknown etiology. This syndrome characterized by pelvic pain and urinary frequency and urgency. Because the signs and symptoms of IC overlap with those of numerous other disorders, it is frequently misdiagnosed as a urinary tract infection, endometriosis, prostatitis, or a number of other conditions. Patients' history and physical examination are essential for diagnostic approach and cystoscopy under anesthesia may be helpful in physicians' decision. Because no specific finding on bladder biopsy can confirm or exclude a diagnosis of PBS, it is not a required component of the diagnostic workup for PBS unless a malignancy is suspected. However, elevated levels of mast cells in the specimen strongly suggest PBS. It is believed that such a clinically oriented approach will facilitate the detection and diagnosis of early and milder disease.