Distraction osteogenesis of the humerus with fully implantable lengthening is now possible since the diameter of the available nails was reduced to 10 mm and below. We report on the first intramedullary lengthening cases of the humerus with two different lengthening devices (FITBONE and PRECICE). Two different approaches and implantation techniques were used. We retrospectively reviewed clinical and radiographic data and pointed out results, pitfalls and complications of the procedure. Four adult patients with relevant length discrepancy of the humerus were treated with fully implantable systems in two centers between 2012 and 2015. Three patients were treated with FITBONE by an antegrade approach; one patient had lengthening with a PRECICE and a retrograde approach. Average nail lengthening was 55 mm (40–65 mm), and the average duration of lengthening was 70 days (52–95 days). The average distraction index was 0.72 mm/day (range 0.4–1.0 mm/day) or 12.5 days/cm (range 8.0–16.2 days/cm). The average consolidation index was 33.6 days/cm (range 25–45 days/cm). There was an implant failure (arrest) with the PRECICE. After consolidation and exchange with a technically improved implant, the course of treatment was uneventful. In patients with antegrade lengthening shoulder abduction decreased, and in the patient with the retrograde approach it improved but elbow extension decreased marginally. Reduced motion of the adjacent joints can be a major problem in intramedullary lengthening of the humerus. This first case series in the field of a rare indication suggests that lengthening of the humerus by fully implantable lengthening nails might be a valuable alternative to lengthening with external fixation. Main advantage of the PRECICE technology is the possible shortening in-between of lengthening.