This study investigates the behavior of chemical elements and the performance of chemical indices within and between weathered pyroclastic and granitic profiles. The profiles were developed under humid, relatively well-drained conditions in Hong Kong. Levels of chemical heterogeneity of the profiles are assessed, and their adverse effects on the selection and use of chemical indices are discussed. Distribution of the chemical elements varies significantly within and between the profiles. At the early stages of weathering, behavior of the elements is fairly predictable and largely controlled by the degree of weathering. At the advanced stages, however, behavior of the elements can be erratic and appears to be governed by micro-environmental conditions and the degree of weathering. Based on the nature of the chemical elements displaying unpredictable distribution along the weathered profiles, two groups of elements are identified. The first group includes K and Al together with loss-on-ignition content. Their variation can be explained in terms of the type and abundance of clay minerals. The second group comprises Fe and Mn, and their unexpected behavior can be correlated with the irregular distribution of sesquioxide-rich zones. Micro-environmental conditions, which govern the type and abundance of clay minerals and sesquioxides, ultimately determine the level of chemical heterogeneity of the profiles. Parent-normalized major element variation diagrams are useful tools for assessing the level of chemical heterogeneity of the profiles. Overall, the pyroclastic profile displays a higher level of heterogeneity than the granitic profile. Performances of chemical indices are particularly poor where a high level of chemical heterogeneity exists. Similarly, chemical indices based on the elements displaying similar geochemical behavior or the degree of decomposition of a single mineral (e.g., plagioclase) will not remain valid over the entire course of weathering. Given that each profile has its own way of responding to weathering processes, the search for a universally accepted ‘best chemical index’ is likely to disappoint. Recognizing the significance of the processes and products of weathering in controlling behavior of the chemical elements, however, and thus in generating chemical heterogeneities helps to avoid random or subjective selection of chemical indices and to interpret unforeseen deviations.