Background: Cow's Milk protein allergy (CMA) is a common finding in infants and young children (2-3%). Its diagnosis is a multifaceted aspect including medical history, clinical examination, diagnostic elimination diets, oral challenge tests (OCT), skin prick tests (SPTs) and specific immunoglobulin E (sIgE) measurements. We aimed to assess the value of SPT and sIgE for diagnosis of infants with CMA in routine clinical practice. Methods: This cross-sectional study included 102 infants with suspected CMA. They were subjected to OCT, SPT with pasteurized cow's milk and measurement of serum sIgE for cow's milk by immunoblot technique. Results: Seventy-two infants (70.59%) showed positive allergic reactions with OCT. Comparing SPT to OCT, sensitivity was 75%, specificity was 68.7%, predictive value for negative (PVN) was 59% and predictive value for positive (PVP) was 93.1%. Comparing sIgE to OCT, sensitivity was 68.1%, specificity was 96.7%, PVN was 69% and PVP was 98%. Comparing both SPT and sIgE together to OCT, sensitivity was 62.5%, specificity was 96.6%, PVN was 51.8% and PVP was 97.8%. Conclusions: For clinical practice, our findings suggest that correlation between SPT and sIgE is significant regarding CMA diagnosis. Therefore, these tests can be used together for diagnosis of CMA. However, still some cases can be only diagnosed with positive OCT with non-detectable sensitization. Therefore, a detailed history is a major factor in assessing CMA. In addition, definition of new optimal cut-offs for sIgE and SPT to cow's milk can improve the accuracy of these tests, hoping to avoid unnecessary and potentially dangerous OTC.