We describe the epidemiology, diagnosis, and management of nontuberculous mycobacterial lymphadenitis cases detailed in a 28-year (1996–2023) multicenter cohort from Spain. The case numbers remained stable during the initial prospective phase (2013–2020), but a sharp decline was observed during 2021–2022. Disease onset occurred during spring or June in 45.9% of cases. Mycobacterium avium complex (43.1%) and M. lentiflavum (39.9%) were the most common species detected. M. lentiflavum affected mostly younger children from central Spain. The most common treatment strategy was complete surgical resection with (n = 80) or without (n = 88) antimicrobial drug treatment, followed by antimicrobial drugs alone (n = 76). Facial palsy developed in 10.4% of surgical cases. Adverse events because of antimicrobial drugs were uncommon. New fistula formation during follow-up occurred more in children managed with observation alone than in those treated with antimicrobial drugs alone (relative risk 2.7 [95% CI 1.3–5.3]; p = 0.014).