Multisystemic inflammatory syndrome (MIS-C) diagnosis remains difficult because the clinical features overlap with Kawasaki disease (KD). The study aims to highlight the clinical and laboratory features and outcomes of patients with MISC whose clinical manifestations overlap with or without KD. This study is a retrospective analysis of a case series designed for patients aged 1 month to 18 years in 28 hospitals between November 1, 2020, and June 9, 2021. Patient demographics, complaints, laboratory results, echocardiographic results, system involvement, and outcomes were recorded. A total of 614 patients were enrolled; the median age was 7.4 years (interquartile range (IQR) 3.9–12 years). A total of 277 (45.1%) patients with MIS-C had manifestations that overlapped with KD, including 92 (33.3%) patients with complete KD and 185 (66.7%) with incomplete KD. Lymphocyte and platelet counts were significantly lower in patients with MISC, overlapped with KD (lymphocyte count 1080 vs. 1280 cells × μL, p = 0.028; platelet count 166 vs. 216 cells × 103/μL, p < 0.001). The median serum procalcitonin levels were statistically higher in patients overlapped with KD (3.18 vs. 1.68 µg/L, p = 0.001). Coronary artery dilatation was statistically significant in patients with overlap with KD (13.4% vs. 6.8%, p = 0.007), while myocarditis was significantly more common in patients without overlap with KD features (2.6% vs 7.4%, p = 0.009). The association between clinical and laboratory findings and overlap with KD was investigated. Age > 12 years reduced the risk of overlap with KD by 66% (p < 0.001, 95% CI 0.217–0.550), lethargy increased the risk of overlap with KD by 2.6-fold (p = 0.011, 95% CI 1.244–5.439), and each unit more albumin (g/dl) reduced the risk of overlap with KD by 60% (p < 0.001, 95% CI 0.298–0.559). Conclusion: Almost half of the patients with MISC had clinical features that overlapped with KD; in particular, incomplete KD was present. The median age was lower in patients with KD-like features. Lymphocyte and platelet counts were lower, and ferritin and procalcitonin levels were significantly higher in patients with overlap with KD.What is Known:• In some cases of MIS-C, the clinical symptoms overlap with Kawasaki disease.• Compared to Kawasaki disease, lymphopenia was an independent predictor of MIS-C.What is New:• Half of the patients had clinical features that overlapped with Kawasaki disease.• In patients whose clinical features overlapped with KD, procalcitonin levels were almost 15 times higher than normal.• Lethargy increased the risk of overlap with KD by 2.6-fold in MIS-C patients.• Transient bradycardia was noted in approximately 10% of our patients after initiation of treatment.