Infections granuloma is a kind of chronic hyperplastic inflammation which is rarely caused by Actinomyces and Nocardia. As clinical symptoms and physical examination results of infectious granuloma caused by Actinomyces and Nocardia are similar, it is easily to lead to misdiagnosis or missed diagnosis. Here we presented a case of infectious granuloma caused by Actinomyces and a case of infectious granuloma caused by Nocardia. The final diagnosis was confirmed by pathological examination, bacterial culture and identification, and gene sequencing. We also summarized the etiology, epidemiology, clinical features, differential diagnosis, treatment and recent advances in these two infections, which could help to make the correct diagnosis without delay and choose the optimal treatment. There two infections have many similarities, and we need to distinguish them for proper therapy. The differential diagnosis with other granulomatous infections, such as tuberculosis, cutaneous sporotrichosis or chromoblastomycosis was also discussed.