Purpose: Acute appendicitis (AA) is one of the most frequent causes of abdominal surgery encountered in emergency rooms. However, reactive lymphoid hyperplasia (RLH) is one of the appendicular pathologies often misdiagnosed. It is quite challenging to distinguish between AA and RLH in terms of planning treatment in an emergency. Therefore, this retrospective study aimed to compare the histological and laboratory findings of AA and RLH. Methods: The retrospective data included in the study were obtained from patients diagnosed with AA. Complete blood count (CBC) and C-reactive protein (CRP) levels of patients with AA and RLH were compared before the surgery based on the histological diagnosis of the patients. Results: A total of 187 patients who previously underwent appendectomy were included in the study. Histopathological examination revealed that 152 patients (81.3%) were diagnosed with AA, and 35 (18.7%) with RLH. While white blood cell count (P < 0.001), neutrophil (P < 0.001), and neutrophil/lymphocyte ratio (P < 0.001) were found to be significantly higher in those with AA; lymphocyte (P = 0.003) and eosinophil counts (P = 0.033) were detected to be significantly higher in those with RLH. CRP level was also significantly higher in those with AA (P = 0.002) Conclusion: We consider that CBC and CRP levels may be predictive in distinguishing between AA and RLH. We consider that these parameters may be valuable in making a distinction between patients before surgery.