The current investigation made an attempt to study the contributory effect of language proficiency, discipline-related knowledge, and content specificity on Iranian EAP students' performances on neighboring and non-neighboring reading comprehension tests. To this end, 160 graduates and undergraduate students of biology and psychology, both male and female holding BA, MA, and PhD degrees were selected through snowball sampling from different universities of Iran including Maragheh, Semnan, Babolshahr, Urmia, Saveh, Tabriz, Tehran, Zanjan to participate in the quantitative study. All the participants were administered five online tests including Vocabulary Level Test (VLT), two Farsi knowledge tests, and two content cloze tests. A mixed factorial ANOVA was used to analyze the collected data. The results indicated that the contributory effect of English proficiency on Iranian ESAP students’ reading comprehension is significantly fluctuated with changes in content specificity of ESAP reading tests. Furthermore, it was concluded that content specificity may be something beyond text difficulty which measured by quantitative indices. Therefore, there is an open question of what content specificity is. The findings of the present study have implications for test developers and researchers in the field ESAP assessment.