This study aims to evaluate the diagnostic accuracy of CA-125 and PET/CT in detecting cancer among adult patients with idiopathic inflammatory myopathy (IIM). We conducted a retrospective study of a single-centre cohort of adult IIM patients enrolled from 2003 to 2020. Data on CA-125 and PET/CT tests conducted within five years of IIM symptom onset were extracted from electronic medical records. The outcomes assessed included true positive, false-positive, true negative, and false-negative results. Among 1432 patients with IIM, 250 CA-125 tests were conducted on 205 patients within the first five years of symptom onset, yielding a false-positive rate of 3.1% and a false-negative rate of 14.3%. Most false positives were associated with endometriosis or uterine fibroids, but additional medical procedures were often carried out to investigate the false-positive results. For PET/CT, 149 tests were performed on 139 patients, resulting in a false-positive rate of 5.5% and a false-negative rate of 28.6%. Lymphadenopathy and lung nodules were the predominant causes of false positives, while melanoma, low-stage breast cancer, and prostate cancer were the most frequent cancers missed (false negatives). False positive and false-negative results are prevalent in CA-125 and PET/CT testing for adult patients with newly diagnosed idiopathic inflammatory myopathy. Understanding the causes of these inaccuracies can aid clinicians in making informed decisions during patient care.