The pathogenesis of eosinophilic esophagitis (EoE) is incompletely understood. In certain eosinophilic diseases, activation of tyrosine kinase after fusion of the Fip1‐like‐1 and platelet‐derived growth factor receptor‐α genes (F‐P fusion gene) mediates eosinophilia via downstream effectors such as extracellular‐regulated kinase (ERK1/2) and signal transducers and activators of transcription (STAT5). This mechanism has not been examined in EoE. Our aim was to detect the F‐P fusion gene, pERK1/2, and pSTAT5 in esophageal tissue from patients with EoE, gastresophageal reflux disease (GERD), and normal controls. We performed a cross‐sectional pilot study comparing patients with steroid‐responsive and steroid‐refractory EoE, to GERD patients and normal controls. EoE cases were defined by consensus guidelines. Fluorescence in situ hybridization (FISH) was performed to detect the F‐P fusion gene and immunohistochemistry (IHC) was performed to detect pERK1/2 and pSTAT5 in esophageal biopsies. Twenty‐nine subjects (median age 30 years [range 1–59]; 16 males; 24 Caucasians) were included: eight normal, six GERD, and 15 EoE (five steroid‐refractory). On FISH, 98%, 99%, and 99% of the nuclei in the normal, GERD, and EoE groups, respectively, were normal (P= 0.42). On IHC, a median of 250, 277, and 479 nuclei/mm2 stained for pERK 1/2 in the normal, GERD, and EoE groups, respectively (P= 0.07); the refractory EoE patients had the highest degree pERK 1/2 staining (846 nuclei/mm2; P= 0.07). No trend was seen for pSTAT5. In conclusion, the F‐P fusion gene was not detected with increased frequency in EoE. Patients with EoE had a trend toward higher levels of pERK 1/2, but not STAT5, in the esophageal epithelium, with highest levels in steroid‐refractory EoE patients.