Purpose: To evaluate both the potential usefulness of multidetector computed tomography (MDCT) in diagnosis of acute appendicitis (AA) in patients with atypical clinical presentation and to compare findings with C-reactive protein (CRP) and white cell count (WCC). Materials and methods: MDCT images in 69 patients with atypical presentation of AA were retrospectively reviewed by two readers in consensus. Diagnostic accuracy, sensitivity, specificity, positive and negative predictive values (PPV/NPV) were assessed considering histopathological evaluation as reference. Patients with AA were grouped in nonperforated vs perforated and CRP/ WCC were correlated using both Chi-square-test (χ 2 ) and receiver operating characteristic (ROC) curve analysis. Results: 39 patients underwent surgery and AA was confirmed histopathologically in 29/39 cases (74.4%), showing nonperforated AA (n=23, 79.3%) and perforated AA (n=6, 20.7%). In the remaining 10/39 patients (25.6%) diverticulitis of sigmoid colon was diagnosed (n=3); colitis (n=4); cholecystitis (n=3). Among the other 30/69 patients MDCT was either unremarkable (n=18) or differentials were detected (n=12). Diagnostic accuracy in patients with histopathologically confirmed AA was 95.7%, sensitivity was 90.6%, specificity was 93.6%, PPV was 83.0%, and NPV was 89.8%. All MDCT findings but calcified appendicoliths and CRP/WCC correlated statistical significant when AA was confirmed histopathologically (χ 2 =26.2; p<0.001). In contrary to WCC (p=0.11), CRP was significantly higher in patients with perforated AA than nonperforated AA (p<0.01), demonstrating an optimal cut-off value >121.5 mg/L. Conclusion: MDCT is required immediately to rule out perforation in patients with suspected AA despite atypical clinical presentation and a CRP level >121.5 mg/L.