In this paper, we analyze the process of conceptualization experienced by students in Secondary School when involved in activities in a teaching and learning sequence on the concept of substance, considering the emergence of zones of the conceptual profile. The results point out that the approaches to different modes of thinking of substance enabled the teacher to discuss and confront ideas, leading students to construct or share meanings stabilized in a scientific view. The conceptual profile was an important tool to design activities by creating discursive contexts involving different modes of thinking about substance, which contributed to raising specific discussions involving historical, scientific and social contexts to understand senses and meanings for substances.