Cellulose acetate (CA), viscose, or artificial silk are biocompatible human-benign derivatives of cellulose, one of the most abundant biopolymers on earth. While various optical materials have been developed from CA, optical CA nanomaterials are nonexistent. Here we report on the assembly of a new family of extremely bright fluorescent CA nanoparticles (CA-dots), which are fully suitable for in vivo imaging/targeting applications. CA-dots can encapsulate a variety of molecular fluorophores. Using various commercially available fluorophores, we demonstrate that the fluorescence of CA-dots can be tuned within the entire UV–VIS-NIR spectrum. We also demonstrate excellent specific targeting of tumors in vivo, when injected in zebrafish (xenograft model of human cervical epithelial cancer), and unusually strong exvivo topical labeling of colon cancer in mice utilizing CA folate-functionalized nanoparticles.