Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare but life-threatening drug hypersensitivity reaction. It has recently been shown that those carrying some human leukocyte antigen (HLA) haplotypes are at high risk for the development of DRESS syndrome with some drugs. There is a strong association with HLA-A*32:01 positivity and vancomycin-induced DRESS syndrome. Here, we present two pediatric cases, one Turkish and the other Syrian, both of whom developed DRESS syndrome during the use of multiple antibiotics included vancomycin, and were shown to have HLA-A*32:01 positivity. To determine the causative drug in patients with DRESS syndrome, patch testing can be administered at least six months after the reaction while the lymphocyte transformation test can only be performed in reference centers. Therefore, delays may occur in identifying the causative drug, especially in patients using multiple drugs. As in our patients, it is important to note that screening for HLA-A*32:01 may enable earlier detection of the responsible drug, which is vancomycin.