A detailed protocol for the synthesis of core/shell semiconductor nanocrystal, their encapsulation into phospholipid micelles, their purification and their coupling to a controlled number of small molecules is given. The protocol for the core/shell quantum dot (QD) CdSe/CdZnS synthesis has been specifically designed with two constraints in mind: green and reproducible core/shell QD synthesis with thick shell structure and QDs that can easily be encapsulated in poly(ethylene glycol)-phospholipid micelles with one QD per micelle. We present two procedures for the QD purification that are suitable for the use of QD micelles for in vivo imaging: ultracentrifugation and size-exclusion chromatography. We also discuss the different coupling chemistry for covalently linking a controlled number of molecules to the QD micelles. The total time durations for the different protocols are as follows: QD synthesis: 6 h; encapsulation: 15 min; purification: 1-4 h; coupling: reaction dependent.