Insulin-derived amyloidosis is a skin-related complication of insulin therapy and is caused by the insulin amyloid deposits at the insulin injection sites. Insulin-derived amyloidosis causes poor glycemic control and increased insulin dose requirements because of impaired insulin absorption at the amyloid sites. There are two forms of insulin-derived amyloidosis, with and without palpable masses. Insulin-derived amyloidosis with a palpable mass may often be called “insulin ball”. Lipohypertrophy is another skin-related complication of insulin therapy and is common in patients on insulin treatment. Insulin-derived amyloidosis and lipohypertrophy are often confused because they have similar characteristics and may coexist. Since insulin-derived amyloidosis and lipohypertrophy interfere with insulin therapy, it is important to prevent them. The greatest risk factor for insulin-derived amyloidosis and lipohypertrophy is the repeated insulin injections at the same site. Therefore, it is necessary to regularly observe the insulin injection sites and repeatedly educate the correct insulin injection methods. For this purpose, not only physicians but also medical staff need to cooperate.