Background: Melanoma incidence is growing worldwide. Although recent advances in imaging, there isn`t still available a specific melanoma agent that can be used for melanoma staging. Archaeosomes may be defined as liposomes composed of one or more polar lipids extracted from the Archaea domain (Archaebacterium). Objective:  As liposomes have been used as vehicles for drugs and isotopes, the aim of this work was to 99mTc radiolabel archaeosomes and evaluates its potential role as a melanoma imaging agent.Methods: Archaeosomes were prepared by hand shaken method and were radiolabeled with 99mTc; Radiolabelling efficiency and purity was evaluated through different chromatographic systems. In vitro stability of 99mTc-DTPA-archaeosomes was performed through L-cysteine challenge.Results: Archaeosomes size distribution was determined by laser light scattering, having nanometer size between 90 and 120 nm. Radiolabelling efficiency was greater than 90%; 99mTc-DTPA-Archaeosomes presented a radiochemical purity superior to 80% evaluated 24 hours post radiolabelling. For the highest concentration of L-cysteine (30mM) and 1h incubation, radiochemical purity was 92.90 %, 6.41 % was bound to cysteine and 0.69 % remained as 99mTcO4- . Biodistribution and scintigraphic imaging studies in healthy C57 black mice showed high liver, spleen uptake and renal elimination. Melanoma bearing mice, had similar biodistribution as healthy mice but increased melanoma uptake, with T/M ratio of 46 ±3.7.Conclusions:  Our results show the feasibility of 99mTc radiolabelling archaeosomes and their potential role as a melanoma imaging agent.