The work reported here involved a comparative study regarding the understanding that high school students (16–18 years) have of the concept of chemical elements and their periodic classification. More specifically, the level of knowledge on this topic was compared before and after the completion of baccalaureate studies in a sample of Spanish students. In order to achieve this goal, a questionnaire was developed that included 14 items in an open format, through which various aspects of the students’ understanding of the idea of chemical element and their periodic classification were assessed. In addition, the application of this knowledge to interpret and predict the behaviour and properties of elements and to carry out calculations on the atomic composition of the elements was evaluated. Aspects concerning the acquisition of scientific knowledge, the application of knowledge to different contexts and situations, and the use of scientific evidence to draw conclusions and knowledge about the nature and history of science were evaluated. The questionnaire was previously validated with a large group of students. The results of this study show that improvements occur primarily in addressing higher level cognitive questions (analysis, synthesis and evaluation) in comparison to the lower level tasks (capacity for retention, understanding or direct application of learning). In addition, students who start high school have a very limited understanding of the ideas behind the Periodic Table of the chemical elements and that their lack of understanding, to a large extent, remains upon completion of the baccalaureate. These results suggest that there are real difficulties in understanding this topic and show the limited influence of the studies completed in high school.