The aim of the present study is to compare the science competencies that students need to demonstrate during school examinations on the one hand and when they participate in PISA on the other. Through their comparison similarities and differences will be detected. To this end, 1.357 test item sets relative to the subject of Biology used in the Gymnasium examinations (lower secondary education) and 50 PISA science items from the category “living systems” and the context life, health, environment were analyzed. The results of the comparative analysis indicate a clear differentiation between the competencies that students need to demonstrate during the school examinations of Biology in Gymnasium and the competencies that students need to demonstrate in order to answer the PISA items correctly. The fact that students have to demonstrate unfamiliar competencies during their participation in PISA could be a factor –among others– that explains the low performance of Greek students in the PISA study.