A controlled study was carried out in this work to decouple the effects of the hydrocarbon chains and the type of hydrophilic groups of the collectors on their collecting ability for minerals with different particle sizes. A high purity niobium oxide (pyrochlore) sample, with two different sizes (medium size of 64 µm and 16 µm, respectively), were floated by four anionic collectors, whose hydrocarbon chain was either octyl or oleoyl and hydrophilic group was either carboxylate or hydroxamate. The four combinations were: octyl hydroxamic acid (OHA), sodium octanoate (C₈OONa), oleoyl hydroxamic acid (C₁₈HA) and sodium oleate (NaOl). Through small-scale flotation tests, it was observed that the carboxylate-based collectors were inferior to hydroxamate-based collectors. Sodium octanoate could not float either the coarse or the fine pyrochlore. Replacing the octyl group in octanoate with a longer hydrocarbon chain, sodium oleate could float the coarse pyrochlore well but its effectiveness dropped sharply when floating the fine pyrochlore. Interestingly, the two hydroxamate-based collectors, octyl hydroxamic acid and oleoyl hydroxamic acid, showed excellent collecting ability to both the coarse and the fine pyrochlore tested. While FTIR analysis showed that all tested collectors adsorbed through chemisorption, isothermal titration calorimetry (ITC) measurements showed a positive correlation between the adsorption affinity and fine pyrochlore flotation recoveries. It is concluded that while the longer hydrocarbon chain of the collector benefited flotation recovery of relatively coarse size particles, for effective fine particle flotation, collectors need to have a hydrophilic group that has a strong affinity to the mineral surface. This work provided useful insights into collector molecular structure design and selection for improved flotation performance of minerals with specific particles sizes.