© 2018 Japanese College of Cardiology Background: Although cardiac sarcoidosis is associated with poor prognosis, diagnosis of the disease is challenging and the sensitivity and specificity of diagnostic modalities are limited. This study was performed to evaluate the potential of serum microRNAs (miRNAs) as diagnostic biomarkers for cardiac sarcoidosis. Methods: We performed genome-wide expression profiling for 2565 miRNAs (Human-miRNA ver.21) using peripheral blood samples from 5 patients with cardiac sarcoidosis (61 ± 9 years) and 3 healthy controls (54 ± 7 years). From this screening study, we selected 12 miRNAs that were significantly related to cardiac sarcoidosis. Next, we performed real-time polymerase chain reaction (PCR) on blood samples from 15 new patients with cardiac sarcoidosis and 4 healthy controls to quantify the expression of these 12 miRNAs. Results: In the screening study, 12 miRNAs were differentially expressed (p < 0.01) in all 5 patients with cardiac sarcoidosis, showing greater fold-change values (>4 or <0.25) compared with the expression in the 3 healthy controls. Analysis of the real-time PCR for blood samples from the other 15 patients and 4 controls using Mann–Whitney U tests revealed that the expression of miR-126 and miR-223 was significantly higher in the patients than in the healthy individuals. However, there were no differences in the expressions of miRNA-126 and miR-223 between patients with only cardiac lesions and those with extra-cardiac lesions. Conclusions: Our results demonstrate the potential of serum miR-126 and miR-223 as new-generation biomarkers for the differential diagnosis of cardiac sarcoidosis in patients with heart failure.