Rare earth elements (REE) have been used in industrial, geological, medical, and agricultural applications. For this reason, the mineral reserves exploration has increased significantly in the last years, which can naturally lead to an increase of the concentration of these elements in soil, water, and consequently in living beings. Given possible exposures, REE has been listed as “New and Emerging Risks to Occupational Safety and Health” by the European Agency for Safety and Health at Work (EU-OSHA). Some studies have been reported, showing the possible biological alterations to REE exposition in living organisms. Ca²⁺, for example, can replace the La³⁺ in many proteins and enzymes and Gd can inhibit selectively Kuffer cells (present in liver), as well as decrease cytochrome P450 activity in hepatocytes. The presence of REE in blood may be an indication of exposure to these elements. In this way, the development of suitable sample preparation methods for further REE determination in blood is important. However, taking into account the complexity of the matrix, the difficulties for wet digestion, the low REE concentration typically found in blood, as well as the low carbon content and low residual acidity required in digests by plasma-based techniques, the development of an accurate sample preparation is an analytical challenge. Furthermore, the knowledge about interferences is important. In this work, a systematic study of metal interferences (Na, K, and Fe, from 10 to 1000 mg L^-1) in REE determination by inductively coupled plasma mass spectrometry (ICP-MS) with an ultrasonic nebulizer (USN) was performed. The REE determination was performed by using an ICP-MS spectrometer (Elan DRC, Perkin Elmer, Canada) with an USN (U6000AT+, CETAC, Technologies USA). In this work, two sample preparation methods were evaluated: i) Conventional wet digestion in open System (CWD-OS) and ii) Microwave-induced combustion (MIC). CWD-OS method was performed by using a heating block (DK 42, Velp Scientifica, Italy). For the MIC method, a microwave-assisted digestion system (Multiwave 3000, Anton Paar, Austria) equipped with 8 quartz vessels (80 mL), with maximum temperature and pressure of 280 °C and 80 bar, respectively, was used. The determination of carbon content in digests and residual acidity was performed by inductively coupled plasma optical emission spectrometry (Optima 4300 DV, Perkin Elmer, USA) and by titration (836, Metrohm, Switzerland), respectively. Five blood samples were used. In the MIC method, the samples were heighted directly on specific paper (Munktell TFN paper). For CWD-OS, the evaluated concentration of nitric acid ranged from 1.0 to 14.4 mol L^-1. For MIC, the maximum blood mass spotted on filter paper (0.1 to 0.2 g), HNO3 concentration (1.0 to 14.4 mol L^-1), iHNO₃+HCl proportion (1+3, 1+2, and 3+1), and aqua regia concentration (25 to 100%) were evaluated. It was possible to observe signal suppression for all REE with 50 mg L^-1 of Na and K. In the case of Fe, signal suppression was observed with 100 mg L^-1. Thus, the blood mass was limited to 0.4 g for both methods investigated (CWD-OS and MIC). The CWD-OS was not suitable for blood digestion because digests with yellow aspects and solutions with solid residues were obtained. By using the optimized conditions by MIC (0.4 g of sample and 6 mL of absorbing solution (1HNO₃+3HCl proportion) clean digests without solid residues and carbon concentration lower than 25 mg L^-1 were obtained. The accuracy of the MIC method was performed by REE recovery experiments in three concentration levels (0.5, 1.0, and 10 ng g^-1). Recoveries higher than 93% were obtained for all REE. Limits of quantification (LOQs) in the range of 1.0 ng g^-1 (Tb e Tm) to 3.1 ng g^-1 (Ce) were obtained. The REE concentration in blood ranged from 8.2 ng g^-1 (La) to 12.5 ng g^-1 (Ce).