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Background Interactive telemedicine applications have been progressively introduced in the assessment of cognitive and literacy skills. However, there is still a lack of research focusing on the validity of this methodology for the neuropsychological assessment of children with Specific Learning Disorder (SLD). Methods Seventy-nine children including 40 typically developing children (18 males, age 11.5 ± 1.06) and 39 children with SLD (24 males, age 12.3 ± 1.28) were recruited. Each participant underwent the same neuropsychological battery assessing reading accuracy, speed, and comprehension, writing, numerical processing, computation, and semantic numerical sense, twice (once during an in-person session (I) and once during a remote (R) home-based videoconference session). Four groups were subsequently defined based on the administration order. Repeated-measure-ANOVAs with assessment type (R vs. I testing) as within-subject factor and diagnosis (SLD vs. TR) and administration order (R-I vs. I-R) as between-subject factors, and between-group t-tests comparing the two assessment types within each time of administration, were run. Results No differences emerged between I and R assessments of reading accuracy and speed, numerical processing, and computation; on the contrary, potential biases against R assessment emerged when evaluating skills in writing, reading comprehension, and semantic numerical sense. However, regardless of the assessment type, the scores obtained with I and R assessments within the same administration time point overlapped. Discussion These results partially support the validity and reliability of the assessment of children's learning skills via a remote home-based videoconferencing system. Implementing telemedicine as an assessment tool may increase timely access to primary health care and to support research activity.