Recent years have seen increased attention being given to the notion of genre in ELT. In spite of the fact that the impact of genre instruction on writing is well researched, little attempts have been made to investigate whether genre variation can affect learners’ reading comprehension. This study tried to clarify if text genre, proficiency level or their interaction had any effect on the reading comprehension of students. Ninety-three students of medicine took a reading comprehension test which had two types of texts each in a different genre, one medical (ESP) and the other general (EGP). In order to compare their performance on both genres and across proficiency levels, a split-plot ANOVA was applied. The findings indicated that text genre and proficiency level, but not their interaction, had significant effects on the reading comprehension. The participants were more proficient in comprehending EGP texts than ESP ones. This shows the relative superiority of topic familiarity over text structure familiarity in text processing. The inability of readability formulas to exactly mirror text difficulty might be another reason for the outperformance of learners on EGP texts.