Food contact materials (FCM) may contain complex mixtures of estrogenic chemicals. A yeast estrogen screen performed on high performance thin-layer chromatography plates (planar-YES, P-YES) is promising for analysis of such mixtures, as it could allow for better elucidation of effects compared with established methods in microtiter plates. However, the P-YES has not been directly compared with established methods. We compared the performance of a microtiter plate YES (lyticase-YES, L-YES) to P-YES on silica gel HPTLC plates using 17β-estradiol (E2), 20 chemicals representative of migrants from plastic FCM, and three migrates of coated metal food cans. Effective doses (ED₁₀, ED₅₀) and estradiol equivalencies were calculated for each chemical. Thirteen chemicals had calculable EDs in the L-YES or P-YES, with average EDs 13-fold (range 0.63–36) more potent in P-YES than in the L-YES. Normalized to E2, the median estrogenicity was within 1.5-fold (0.43-8.8) between the assays. Therefore, P-YES was as or more sensitive than L-YES but potencies relative to E2 were comparable between assays. With chromatography, the P-YES detected estrogenicity in coated metal cans, effects that were unmeasurable in L-YES. With the sample preparation methods used in this study, both YES assays are sufficiently sensitive to detect bisphenol A below the specific migration limit for plastic packaging (0.05 mg/kg food). This study demonstrates that P-YES outperforms L-YES because it is more sensitive, provides comparable estradiol equivalents, and circumvents confounding mixture effects. The P-YES will be useful for routine monitoring of FCM and toxicant identification in problematic materials.