Among 1337 Iranian adult female sex workers in 2015, we assessed the diagnostic value of 4 self-reported sexually transmitted infection (STIs) symptoms for detecting laboratory-confirmed gonorrhea, chlamydia, trichomoniasis, human papillomavirus (HPV), and syphilis. While 37.7% reported vaginal discharge (VD), 25.9% reported pain or burning (P/B), 3.0% reported genital ulcers (GU), and 1.4% reported genital warts (GW), the prevalence of laboratory-confirmed syphilis, gonorrhea, chlamydia, trichomoniasis, and HPV was 0.4, 1.3, 6.0, 11.9, and 41.9%, respectively. The sensitivity of VD was 40.3% for detecting tricomoniasis, 37.5% for chlamydia, and 37.5% for gonorrhea. The sensitivity of P/B ranged from 12.5% for gonorrhea to 25.2% for trichomoniasis. The sensitivity of GU and GW was very low for 5 STIs. The sensitivity of all symptoms combined was also lower than 50%. Among asymptomatic participants, 41.2% tested positive for HPV, 11.8% for trichomoniasis, and less than 6.6% for other STIs. Symptom-based case management and surveillance of STIs can lead to misclassification of a large proportion of cases.