Objective To establish an orthotopic neuroblastoma xenograft model and evaluate it by comparison with the ectopic xenografted model. Methods SCID-Beige mice were used in the study. Neuroblastoma cells were implanted into the fat pad that surrounds the left adrenal gland to establish the orthotopic xenografted model or into the subcutaneous tissue of the right flank for the ectopic xenografted model. After the implantations, the tumor formation rate and size were evaluated at 7, 14, and 21 days, and histopathological analysis was performed. Results After implantation of the same number of neuroblastoma cells, tumors formed in all orthotopic xenografted mice at the three time points, whereas 33%, 67%, and 78% of ectopic xenografted mice had tumors, respectively. The orthotopic xenografted model showed a higher tumor formation rate than the ectopic xenografted model at the three time points. In the orthotopic xenografted model, the tumor volumes were ( 116. 21 ± 78. 82), ( 245. 32 ± 97. 31), and ( 3091. 21 ± 2042. 39) mm³ , whereas the tumor volumes were (7. 26±6. 04), (41. 67±38. 52), and (292. 14±167. 12) mm³ in the ectopic xenografted model at 14, 21, and 28 days, respectively. Orthotopic xenografted tumors were larger than ectopic xenografted tumors at each time point. HE staining showed that the density of orthotopic xenografted tumor was higher than that of ectopic xenografted tumors. Conclusions The orthotopic xenografted model is applicable. Compared with the ectopic subcutaneous xenograft model, the orthotopic xenografted model had the advantages of higher tumor formation and growth rates. These data indicate that the orthotopic xenografted model is a better model for neuroblastoma research.