Objective Teleneuropsychology (TNP) has been shown to be a valid assessment method compared with in-person neuropsychological evaluations. Interest in delivering TNP directly to patients’ homes has arisen in response to the coronavirus disease 2019 (COVID-19) pandemic. However, prior research has typically involved patients tested in clinical settings, and the validity of in-home TNP testing has not yet been established. The present study aims to explore the validity and clinical utility of in-home TNP testing in a mixed clinical sample in the wake of COVID-19. Methods Test profiles for 111 in-home TNP patients were retrospectively compared with 120 patients who completed in-person evaluations. The TNP test battery consisted of tests measuring attention/processing speed, verbal memory, naming, verbal fluency, and visuoconstruction. TNP scores of cognitively normal (CN) patients were compared with patients with neurocognitive disorders (NCD), and score profiles were examined among suspected diagnostic groups of Alzheimer’s disease (AD), Parkinson’s disease (PD), and vascular disease (VaD). Results TNP test scores did not significantly differ from in-person testing across all tests except the Hopkins Verbal Learning Test-Revised Discrimination Index. Within the TNP group, significant differences between the CN and NCD groups were found for all tests, and the memory and semantic fluency tests yielded large effect sizes (d ≥ 0.8). Score profiles among the AD, PD, and VaD groups were explored. Conclusions These findings support the validity of in-home TNP testing compared with in-person neuropsychological testing. Practice considerations, limitations, and future directions are discussed.