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Case Description: A 5-year-old 38.3-kg (84.5-lb) mixed-breed dog was examined because of acute onset of lethargy and anorexia. Four days later, a raised, firm, warm 15 × 10-cm lesion was detected in the right caudal paralumbar area., Clinical Findings: Cephalexin treatment yielded a poor response. Formalin-fixed tissue and fluid samples from the cystic areas of the lesion were submitted for cytologic and histologic examinations, routine bacterial and mycobacterial culture, and genus identification and 16S partial sequencing via PCR assays. Cytologic examination revealed chronic pyogranulomatous inflammation. Histologic examination by use of routine, Giemsa, silver, acid-fast, and modified acid-fast stains revealed multifocal nodular granulomatous panniculitis without identifiable organisms. Mycobacteria were initially identified via PCR assay and mycobacterial culture within 3 days. Mycobaterium goodii was speciated by use of partial 16S RNA sequence analysis., Treatment and Outcome: The lesion resolved after long-term treatment with a combination of rifampin and clarithromycin and insertion of a Penrose drain. There has been no recurrence of the condition., Clinical Relevance: M goodii is an environmental rapidly growing mycobacterium and is a zoonotic pathogen. Infections have not been previously reported in domestic animals in North America, although there are rare reports of infection in humans associated with surgery, especially surgical implants. Domestic animals are a potential sentinel for this non-tuberculous mycobacterial infection in humans, although lack of speciation in infections of domestic animals likely underestimates the potential public health importance of this pathogenic organism. Current microbiological molecular methods allow for a rapid and inexpensive diagnosis.