What major problem did chemists face when applying John Dalton’s atomic theory?

When applying John Dalton’s atomic theory, chemists faced a major problem: they lacked a reliable method to determine the actual number of atoms in a molecule or to unambiguously establish the formulas of compounds.12

Because scientists could not directly weigh individual atoms or molecules, they relied on mass ratios, which were insufficient to distinguish between different substances. Dalton himself assumed a rule of "greatest simplicity," incorrectly believing that the simplest combination of atoms was always the correct one (e.g., assuming water was HO instead of H₂O).312

This uncertainty led to a state of chaos in chemical notation by the mid-19th century, as different chemists assigned conflicting formulas to the same substances. This confusion persisted until the Italian chemist Stanislao Cannizzaro demonstrated in 1858 that Amedeo Avogadro’s earlier hypotheses could be used to construct a consistent and robust system of atomic weights and molecular formulas.31