Purpose To develop a practical scoring system to assist clinicians in differentiating leptospirosis and hantavirus infections, whose epidemiological, clinical, and laboratory characteristics are literally like identical twins. Methods The study population consisted of 162 patients admitted to hospital with a confirmed diagnosis of leptospirosis (LG group, n = 92) and hantavirus infections (HG, group = 70) between January 2000 and January 2019. The two groups were compared in terms of demographic, clinical and laboratory features. Sensitivity, specificity, and positive and negative predictive values were determined from ROC analysis for findings of significance in the diagnosis of leptospirosis, and a scoring system for diagnosis was developed ("MICE" score). During the development of this scoring system, we were careful to employ parameters that would not affect one another statistically, to reflect the involvement of very different systems (such as the hematological, hepatic, renal, and musculoskeletal systems) due to the multisystemic effect of the disease in the organism, and to ensure that the system should be simple to apply and understand. Accordingly, five parameters, serum WBC, creatinine, creatine kinase, total bilirubin, and C-reactive protein, were employed in the "MICE" scoring system. Results Three cut-off values were determined using ROC analysis for the five parameters included in the MICE system. Accordingly, scores of 0, 1, or 2 were given based on the values WBC (/mu L): <= 7500, 7500-15,000, and > 15,000; total bilirubin (mg/dL): <= 3, 3-10, and > 10; CRP (mg/dL): <= 5, 5-15, and > 15; creatinine (mg/dL): <= 1.5, 1.5-3, and > 3; CK (U/L): <= 500, 500-1000, > 1000. AUC was calculated as 0.964 at ROC analysis, while the most noteworthy cut-off point was obtained when MICE score was >= 3, exhibiting 93.5% sensitivity, 92.9% specificity, PPV 94.5% and NPV 91.5%. A test score >= 3 was regarded as positive. In addition, our patients were evaluated using other current scoring systems in addition to "MICE," and our scoring system exhibited a greater diagnostic power in our subjects. Conclusions Leptospirosis and hantavirus infections can be accurately predicted by the MICE scoring system. Early diagnosis and rational treatment will also help to lower the mortality rates in these diseases.