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Purpose To measure the influence of best‐fit (BF) algorithms (entire dataset, 3 or 6 points landmark‐based, or section‐based BF) on virtual casts and their alignment discrepancies. Material and methods A mandibular typodont was obtained and digitized by using an industrial scanner (GOM Atos Q 3D 12M). A control mesh was acquired. The typodont was digitized by using an intraoral scanner (TRIOS 4). Based on the alignment procedures, four groups were created: BF of the entire dataset (BF group), landmark‐based BF using 3 reference points (LBF‐3 group), or 6 reference points (LBF‐6 group), and section‐based BF (SBF group). The root mean square (RMS) error was calculated. One‐way ANOVA and post hoc pairwise multi‐comparison Tukey were used to analyze the data (α = 0.05). Results Significant RMS error mean value differences were found across the groups (p < 0.001). Tukey test revealed significant RMS error mean value differences between the BF and LBF‐3 groups (p = 0.022), BF and LBF‐6 groups (p < 0.001), LB‐3 and LB‐6 groups (p < 0.001), LBF‐3 and SBF groups (p < 0.001), and LBF‐6 and SBF groups (p < 0.001). The LBF‐6 group had the lowest trueness, while SBF and BF groups obtained the highest trueness values. Furthermore, significant SD differences were revealed across the groups tested (p < 0.001). Tukey test revealed significant SD differences between the BF and LBF‐6 groups (p < 0.001), LBF‐3 and LB‐6 groups (p < 0.001), LBF‐3 and SBF groups (p = 0.004), and LBF‐6 and SBF groups (p < 0.001). The BF and SBF groups showed equal and highest precision, while the LBF‐6 group had the lowest precision. Conclusions The best‐fit algorithms tested influenced the virtual casts’ alignment discrepancy. Entire dataset or section‐based best‐fit algorithms obtained the highest virtual casts’ alignment trueness and precision compared with the landmark‐based method.