PURPOSE The most significant adverse risk factor for neuroblastoma (NB) is MYCN gene amplification, which strongly associates with high-risk disease. Fluorescent in situ hybridization (FISH) is considered the best method to evaluate MYCN gene status. However, it requires a laboratory that can perform highly complex testing, specialized personnel, and costly reagents. Herein, we aimed to investigate the feasibility of using immunohistochemistry (IHC) to detect MYCN protein expression in lieu of FISH, a strategy potentially useful in areas with limited resources. METHODS A pilot cohort of 78 patients with NB, including 34 of Middle Eastern descent (MED) who had a higher prevalence of MYCN gene amplification (44.11%) and 44 of North American descent (NAD), nine (20.45%) of whom had MYCN amplification, was evaluated with IHC for MYCN protein. Correlations of FISH results and protein expression are presented. RESULTS A positive correlation between MYCN gene amplification and protein expression by IHC was seen in 22 (91.66%) of the 24 MYCN-amplified NB cases—14 (93.33%) of 15 patients of MED and eight (88.88%) of nine patients of NAD. Agreement between negative FISH and negative IHC results was noted in 18 (94.73%) patients of MED and 34 (97.14%) patients of NAD. Two cases had weak protein expression but no gene amplification (MED: n = 1; 5.0%; NAD: n = 1; 2.9%). CONCLUSION An excellent overall correlation between MYCN gene status by FISH and MYCN protein expression by IHC was confirmed. MYCN IHC in NB with reflexing to FISH in equivocal cases is potentially useful in a limited-resource setting. Evaluation of effectiveness using a larger cohort and optimization to perform MYCN IHC manually is needed.