A 13-year-old girl presented with abdominal pain. A thorough examination revealed the presence of multiple masses throughout the patient's body . Magnetic resonance imaging (MRI) scans revealed multiple areas of bone destruction in the following anatomical regions: the cranium, the cervical spine, the thoracic spine, the lumbar spine, both humeri, the clavicles, the scapulae, and the ribs. Multiple abnormal signals were observed in the liver and spleen. Further investigative procedures, encompassing complete blood count, blood biochemistry , and tumor markers, yielded no substantial anomalies.Concurrently , a cystic mass measuring 5 cm in diameter was identified in the left axilla. Biochemical analysis of the white chylous fluid aspirated from the cyst revealed no abnormalities. The surgical biopsy revealed microscopic histopathology , showing irregularly sized, proliferating lymphatic vessels within the adipose tissue. Immunohistochemistry was utilised to confirm a diagnosis of lymphatic malformation. Molecular testing via next-generation sequencing (NGS) identified an STRN::ALK fusion mutation,which was classified as a somatic mutation devoid of hereditary characteristics. Following a comprehensive diagnosis, targeted therapy with oral crizotinib was initiated. The most recent clinical follow-up has demonstrated favourable outcomes, with effective control of multiple systemic tumours, as confirmed by imaging studies. Generalized Lymphatic Anomaly (GLA) is a rare congenital multisystem disorder that originates in the lymphatic system. This constitutes the first reported case of STRN-ALK fusion lymphangiomatosis treated with targeted therapy against the ALK gene.