A term newborn presented with widespread cutaneous erythematous to bluish lesions since birth. He had extensive lesions in the gastrointestinal tract, brain, retina, heart, and bones. He also developed an intestinal perforation due to erosion of an intestinal lesion. Due to his critical status and clinical presentation, he was initially diagnosed with multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT), and sirolimus treatment was initiated. Sirolimus was given by buccal route in this nonfeeding patient. Therapeutic serum levels were obtained comparable to enteral administration. Buccal mucosa was an effective novel route of sirolimus administration in this patient.