We compare the utility of core biopsy samples with surgical tumor specimens as starting material for microarray analysis. Two human tumor xenografts, Ewing sarcoma and neuroblastoma grown in Beige-Scid mice, served as source materials for this study. Six 16g-needle core biopsies and an excision biopsy were performed on each xenograft. Three of the six core biopsies were processed separately and the other three were pooled together. As the initial material isolated from the core biopsies was not sufficient for microarray analysis, we performed an amplification procedure using a modified Eberwine protocol. A complementary DNA microarray consisting of 6,000 human genes was used. Comparison of the array results from core biopsies (amplified RNA) and surgical specimens (non-amplified RNA) showed maintenance of the expression profile and concordance in identifying outliers in the range of 58%. This finding compares with a 48–77% concordance observed among three different samples of the same excisional biopsy using total RNA. The level of concordance was higher when an amplified core biopsy was compared with an amplified excisional biopsy: 64% for the Ewing sarcoma and 83% for the neuroblastoma. Pooling the core biopsies did not improve the concordance with surgical biopsies. Gene expression profiles obtained from microarray analysis differentiated Ewing sarcoma from neuroblastoma with both core and surgical biopsies as starting material. Our results suggest that core biopsy samples can be used as acceptable and reliable material for the determination of tumor genetic profiles.