Background: The differential diagnosis of lymphadenopathies in children including benign and malignant conditions is often difficult to identify by ultrasound (US). The lymphadenopathies in children are frequent and mostly benign, therefore it is essential to decide what patients should undergo further studies. Objective: To describe the potential usefulness of a new suspicious ultrasound sign on pediatric lymphadenopathies that can orient the diagnosis of malignancy. Materials and methods: We retrospectively reviewed all pediatric cases with lymphadenopathy suspicious of lymphoma or lymphoproliferative syndrome on soft tissue ultrasound from 2014 to 2021. Two expert ultrasound radiologists reviewed ultrasound images of these patients, associating the internal structure of infiltrated adenopathy with the internal structure of the truffles. Results: On ultrasound, twelve cases presented enlarged lymphadenopathy with loss of internal structure, without hilum; mostly hypoechoic parenchyma, with some fine echogenic serpiginous linear surrounding hypoechoic pseudo nodular images, resembling the inner structure of black truffles. This US pattern looked suspicious and histological study was recommended. In 9 cases a lymphomatous infiltrated adenopathy was confirmed on biopsy. Conclusion: The truffle sign is a new potential suspicious ultrasound sign, that can suggest malignant lymphadenopathy in children. This ultrasound pattern can have some probable usefulness to the radiologist in order to recommend further studies, including histological study, that need to be validated by a larger sample. It is important to recognize easily and early the lymphomatous compromise in a lymph node.