Background: beta-D-glucan (BDG) is a helpful diagnostic marker for many invasive fungal infections, but not for nocardiosis. Here, we reported the first case of nocardial infection with high serum level of BDG. Case presentation: A 73-year-old man was hospitalized because of fever, headache, and appetite loss after 10 months of steroid and immunosuppressive therapy for cryptogenic organizing pneumonia. With a diagnosis of bacterial pneumonia, treatment with ampicillin/sulbactam was initiated. There was improvement on chest radiograph, but fever persisted. Further work-up revealed multiple brain abscesses on cranial magnetic resonance imaging (MRI). Serum galactomannan and BDG were elevated at 0.6 index and 94.7 pg/ml, respectively. Voriconazole was initiated for presumed aspergillus brain abscess. However, fever persisted and consciousness level deteriorated. Drainage of brain abscess was performed; based on the Gram stain and Kinyoun acid-fast stain, disseminated nocardiosis was diagnosed. Voriconazole was then shifter to trimethoprim/sulfamethoxazole. The presence of Nocardia farcinica was confirmed by the 16S rRNA gene sequence. Treatment course was continued; BDG level normalized after 1 month and cranial MRI showed almost complete improvement after 2 months. Conclusion: BDG assay is widely used to diagnose invasive fungal infection; therefore, clinicians should be aware that Nocardia species may show cross-reactivity with BDG assay on serum.