Tandem repeats (TRs) are DNA regions of tandemly repeated nucleotide motifs. Their pathogenic expansions cause various, mainly neurologic, diseases.We analyzed 65 TR loci using ExpansionHunter in individuals who underwent short-read whole-exome sequencing (WES) or whole-genome sequencing (WGS) for the diagnosis of a rare neurologic condition.Of 1,106 proband samples (1,053 WES, 53 WGS), we detected 232 TR expansions in the intermediate or pathogenic range in 18.7% (207/1,106). However, 51 TR expansions were revised as false positives (FPs) and 83 as nondisease-causing. Of the 98 disease-causing TR expansions, 5 were classified as causal hemizygous or heterozygous TR expansions associated with X-linked recessive (XLR) or autosomal dominant (AD) neurologic disorders in 5 probands (0.5%). The low incidence is due to the fact that individuals with typical clinical symptoms (spinocerebellar ataxia) were tested for TR expansion by conventional laboratory methods. Only 1 proband with clinical suspicion of spinal and bulbar muscular atrophy was fully explained by TR expansion in the AR gene, and in 4 others, we hypothesize the possible involvement of 2 different neurologic diseases. Another 82 causal hemizygous or heterozygous TR expansions associated with XLR or AD non-neurologic diseases (secondary findings) were identified in 81 probands (7.3%), of which 70 expansions in TCF4 were associated with Fuchs endothelial corneal dystrophy, a common eye disease in older patients. Finally, we detected 11 heterozygous TR expansions for XLR and autosomal recessive (AR) diseases in 11 probands who had no clinical symptoms of the associated TR disease.The unexpectedly high detection rate (18.7%) of TR expansions necessitates the filtration of FPs and nondisease-causing expansions, thereby underscoring the necessity of visual inspection of ExpansionHunter results. The study demonstrated that both WES and WGS diagnostics can benefit from TR expansion analysis. The secondary findings indicate that the previously published pathogenic ranges of TR expansions in RUNX2 and ZIC3 warrant further investigation.