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BackgroundThe complications of large‐volume fat grafting (LVFG) for breast augmentation remain unpredictable and include palpable breast nodules, oil cysts, and calcifications.AimsThis study was aimed to provide an optimal treatment option for breast nodules after LVFG and evaluate their pathological characteristics.Patients/MethodsWe effectively performed complete resection of breast nodules in 29 patients after LVFG using a minimal skin incision with the vacuum‐assisted breast biopsy (VABB) system under ultrasound guidance. And we further carried on histologic examination of excised nodules and evaluated their pathological characteristics.ResultsThe breast nodules were excised thoroughly with cosmetic effect satisfactorily. Interestingly, subsequent histologic examination showed that type I and VI collagens were strongly expressed in the fibrotic area and type IV collagen were positively expressed around the blood vessel. Furthermore, we found that the type VI collagen+ area appeared around mac2+ macrophages and α‐SMA+ myofibroblasts.ConclusionsThe VABB system may be the optimal treatment option for breast nodules after LVFG. And type VI collagens may serve as a biomarker of grafted adipose tissue fibrosis. The relationship between macrophages, fibroblasts, and collagen formation may be therapeutic targets for regulating fibrosis.